RO114254B1 - Substituted derivatives of 2-/(4-heterocyclicphenoxymethyl)phenoxy/alkanoates - Google Patents

Abstract

Herbicidal compounds, compositions containing them, and a method for controlling weeds by application of the compositions are disclosed. The herbicidal compounds are 2-[(4-heterocyclic-phenoxymethyl)phenoxy]alkanoates of the formula <IMAGE> in which A is a derivative of an alkanoate bonded to the phenoxy oxygen at the alpha carbon, and Q is 4-difluoromethyl-4,5-dihydro-3-methyl-l,2,4-triazol-5(1H)-on-1-yl, 3,4,5,6-tetrahydrophthalimid-1-yl, 1-(1-methylethyl)imidazolidin-2,4-dion-3-yl, 1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-on-1-yl, 3-chloro-4,5,6,7-tetrahydroindazol-2-yl, 4-methyl-l,2,4-triazine-3,5-dion-2-yl, 8-thia-1,6-diazabicyclo[4.3.0]-nonane-7-on-9-ylimino, or 1-methyl-6-trifluoromethyl-2,4-pyrimidinedione-3-yl; X is hydrogen, methyl, fluorine, or chlorine; Y is hydrogen; W is oxygen or sulfur; Z is hydrogen, fluorine, chlorine, bromine, lower alkyl, or methoxy; Z' is hydrogen, fluorine, or chlorine; and the group AO- may be in the 2, 3, or 4-position of the phenyl ring.

Description

The invention relates to substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl] phenoxy] alkanoates, especially propionates and acetates, which have herbicidal properties and which can be used for weed control, in agriculture, horticulture and other fields in which it is desired to control unwanted plants, such as herbaceous or large leaf species.

Triazolinone alkanoates of the formula are known:

wherein: R _a is preferably lower haloalkyl and R b is preferably lower alkyl; R _n and R ₂ have different meanings; X and Y are independently halogen, alkyl, alkoxy, alkylthio, haloalkyl, nitro, cyano, sulfonylalkyl or -SOF ₃ ; Z is CH or N; and A is the radical of an alkanoate bound to phenoxy oxygen by carbon alpha. (US 5,084,085]

Other phenoxy-alkanoate heterocyclic derivatives are known, wherein the heterocyclic radical is a 3,4,5,6-tetrahydrophthalimide radical. (US 4,816,065]

Also known are derivatives of the general formula:

wherein: X is hydrogen, halogen, nitro, alkyl or alkoxy; Y is hydrogen, halogen, alkyl, and n and m are each 1 to 4. (US 3,984,434, JP 54-26534 and JP 6039668 and Patent Applications JP 49-000434, 54-19965)

No substituted alkanates were described! of 2,4- (heterocyclyl-phenoxymethyl) phenoxy having strong herbicidal effects, which form the object of the invention.

The object of the invention consists of certain substituted derivatives of 2 - [(4-heterocyclicphenoxymethyl] -phenoxy] -alkanoates, of general formula (I):

in which:

A is R "-C-CHR '

II

I

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Q is 4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5- (1H) -on-1-yl, or 1-methyl-6-trifluoromethyl-2,4- (1H , 3H) -pyrimidin-dion-3-yl; R is hydrogen; M, lower alkyl, cycloalkyl, lower alkenyl or lower alkynyl, each optionally substituted with one or more chlorine, fluorine, or / CHR ₇ - (CH ₂ ) _m 0 / _n F ^; R 'is hydrogen or 50 methyl; R is OR or amino, phenylamino, lower alkylamino, lower alkenylamino, alkoxyamino, cyano or lower alkyl, haloalkyl-lower, or phenylsulfonyl-amino of the formula -Nalphyl lower] -SO ₂ R _g or -NHSO ₂ R _g ; R ₇ is hydrogen or methyl; R ₈ is lower alkyl; R _g is lower alkyl, lower haloalkyl, or phenyl; X is hydrogen, fluorine, methyl or chlorine; Y is hydrogen; W is oxygen or sulfur; Z is hydrogen, fluorine, chlorine, bromine, lower alkyl or methoxy; Z ¹ is hydrogen, fluorine or chlorine; Z and Z ¹ together may be a - (CH ₂ ) 4- group to form a tetrahydronaphthyl radical; m is □ up to 2, and n is 1 to 6; M is sodium, potassium or ammonium; and the group AO- may be in position 2, 3, or 4 of the phenyl ring.

Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl) -phenoxy] - 6o alkanoates of general formula (I), wherein R is -OH, are preferred; X is hydrogen, fluorine or chlorine; and Z is hydrogen, chlorine or lower alkyl.

Other preferred derivatives of 2 - [(4-heterocyclic-phenoxymethyl) -phenoxy] -alkanoates, of general formula (I), are those wherein R is lower alkyl, lower chloralalkyl, or / CHR ₇ - (CH ₂ ) _m 0 / _n R _a ; R 'is methyl; Z is in position 4-; Z 'is hydrogen or chlorine at position 3-; m is O or 1, and n is 1 to 3; and the group AO- is in the 2-position of the phenyl ring, Q is 4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5- (1H) -on-1-yl; R is methyl or CH ₃ (CH ₂ ) ₂ -0- (CH ₂ ) ₂ -; and X is fluorine, and W is oxygen and Z 'is hydrogen; preferably R is methyl, and Z is ethyl, methyl, methylethyl or chlorine, or R is 2- (2-methoxyethoxy) ethyl, and Z is methyl, or R and Z are each methyl, W 70 is sulfur, and Z * is hydrogen.

Particularly preferred are compounds of general formula (I), wherein Q is 1-methyl-6-trifluoro-methyl-2,4- (1H, 3H) -pyrimidindione-3-yl, R is methyl, 2,2, 2-trichloroethyl, or CH ₃ O [CH ₂ ) ₂ -O- (CH ₂ ) ₂ -, W is oxygen, X is hydrogen or fluorine, and Z 'is hydrogen, or those in which R and Z are each methyl and X is hydrogen or fluorine, or 75

R is methyl, X is hydrogen and Z is ethyl, or R is methyl, X is fluorine and Z is ethyl.

Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl] -phenoxy] -alkanoates, wherein the general formula (I), R is 2,2,2-trichloroethyl, X is hydrogen and Z is methyl, or R is 2, 2,2-trichloroethyl, X is hydrogen and Z is ethyl, they are particularly important.So The compounds of the invention can be used in the form of a herbicidal composition, mixed with an agriculturally acceptable carrier, to control the growth of unwanted plants, by applying a herbicide-efficient amount where they grow, or will grow.

The invention has advantages in that it makes certain 2 - [(4- 8 5 heterocyclicsubstituted-3-halo-phenoxymethyl] phenoxy) alkanates, namely those in which the heterocyclic part is selected from the groups: 4-difluoromethyl-4,5-dihydro -3-methyl-1,2,4-triazole-5 (1H) -on-1-yl; 3,4,5,6-tetrahydrophthalimid-1-yl; 1- (1-methylethyl) imidazolidin-2,4- dionRO 114254 Bl

3-yl; 1,4-dihydro-1- (3-fluoropropyl) -5H-tetrazol-5-on-yl; 3-chloro; 4,5,6,7-tetrahidroindazol2-yl; 4-methyl-1,2,4-triazine-3,5-dion-2-yl; 8 tis-1,6-diazaiciclio- / 4.3 A / nonane-7-on-9-ylimino; and 1-methyl-6-trifluoromethyl, 2,4-pyrimidindion-3-yl, compounds that have important herbicidal properties both pre- and post-emergence.

In this specification, the "lower alkyl" group contains 1 to 6 carbon atoms, preferably 1 to 4, the "lower alkenyl" or lower alkynyl groups contain 2 to 6 carbon atoms, preferably 2 to 4, cycloalkyl groups "contain 3 to 6 carbon atoms, and" halogen "or halo" means bromine, chlorine or fluorine, preferably chlorine or fluorine.

Representative compounds according to the invention are exemplified in table 1 below, and the characteristic data of these compounds are given in table 2.

I r ·

R'-CH ₃ , wo

Compound No. Q _a X Y Z Z ' R 1 A H H H H CH _a 2 A F H H H H 3 A F H H H CH 4 A F H 4-F H ch ₃ 5 A F H 3-Cl H ch ₃ 6 A F H 4-Cl H H 7 A F H 4-Cl H ch ₃ 8 A F H 5-Cl H ch ₃ 9 A F H 4-Br H ch ₃ 10 A F H 3-F 4-F ch ₃ 11 A F H 3-Cl 4-Cl ch ₃ 12 A F H 4-CH H ch ₃ 13 A F H 5-0CH ₃ H ch ₃ 14 A BUT H H H ch ₃ 15 A BUT H H H ch ₃ o (CH ₂ ) _a O (CH _? ) p 16 A BUT H 4-F H CHq

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Compound No. Q _a X Y Z Z ' R 17 A BUT H 3-Cl H CHq 18 A BUT H 4-Cl H CH 19 A BUT H 4-Br H CH 20 A BUT H 3-F 4-F CH 21 A BUT H 3-Cl 4-Cl CH 22 A BUT H 4-CH ₃ H CH 2. 3 B H H H H CH 24 B F H H H CH 25 B F H 4-F H CH 26 B F H 3-Cl H CH 27 B F H 4-Cl H CH 28 B F H 5-Cl H CH 29 B F H 4-Br H CH 30 B F H 3-F 4-F CH 31 B F H 3-Cl 4-Cl CH 32 B F H 4-CH H CH 33 B BUT H 4-F H CH 34 B BUT H 3-Cl H CH 35 B BUT H 4-Cl H CH 36 B BUT H 4-Br H CH 37 B BUT H 3-Cl 4-Cl CH 38 B BUT H 4-CH H CH 39 B 3-0C (CH ₃ ) ₂ CH ₂ -2 H H ch ₃ 40 B 3-0C (CH ₃ ) ₂ CH ₂ -2 4-Cl H ch ₃ 41 C F H H H CH 42 C F H 4-F H CH 43 C F H 3-Cl H CH 44 C F H 4-Cl H CH 45 C F H 3-Cl 4-Cl ch ₃ 46 C F H 3-Cl 4-Cl CH

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Compound No. Q _a X Y Z Z ' R 46 A F H 4-Cl 6-Cl ch ₃ 47 A F H 4-CH ₃ H H 48 A F H 4-CH ₃ H c ₂ h ₅ 49 A F H 4-CH ₃ H C- ₃ H ₇ 50 A F H 4-C _p H ₅ H H 51 A F H 4-C _p H ₅ H ch ₃ 52 A F H 4-C ₃ H ₇ H ch ₃ 53 A F H 4-i-C ₃ H ₇ H ch ₃ 54 A F H 4-C ₄ H _q H ch ₃ 55 A F H 4-tC ₄ H _A H ch ₃ 56 A F H 4-C ₂ H ₅ H ch ₃ o ₂ c Hp (CH ₃ 57 A F H 4-CH _a H ch ₃ o (CH ₂ ] ₂ O (CH _P ] _P 58 A F H 4-C ₂ H ₅ H CH ₃ 0 (CH ₂ ) ₂ O (CH _P ) _P 59 A F H 4-tC ₄ H _g H CHgO (CH ₂ ) ₂ □ (CH _P ] _P 60 A F H 4-0 H ch ₃ 61 A F H 3- (CH _p ) ₄ -4 ch ₃ 62 A BUT H 4-C _p H ₅ H ch ₃ 63 D F H 4-Cl H ch ₃ 64 D F H 4-CH ₃ H ch ₃ 65 D F H 4-C _p H ₅ H ch ₃ 66 E F H 4-Cl H ch ₃ 67 E F H 4-CH ₃ H ch ₃ 68 F F H 4-CH ₃ H ch ₃ 69 G F H 4-Cl H ch ₃ 70 G F H 4-CH ₃ H ch ₃ 71 G F H 4-C ₃ H ₇ H ch ₃

R '= CH ₃ ; W = S

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Comp.Nr Q _s X Y Z Z ' R 72 A F H 4-Cl H CH 73 A F H 4-CH H ch.

R '= H; W = 0

Comp.Nr □ _a X Y Z Z ' R 74 A F H H H CH 75 A F H 4-CH H CH 76 A F H 4-CH H H 77 B F H H H CH 78 D F H 4-CH H CH

205

R *

210

215 r * -ch ₃ , vo

220

Comp.Nr Q _a X Y Z Z ' R 79 A F H H H H 80 A F H H H CH

225

230

235

V-CH3, V-0

240

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Comp.Nr X Y Z Z ' R 81 A F H H H CH 82 A F H H H CH ₃ 0 (ch ₂ j ₂ O (CH _P ) _? 83 A Cl H H H CH 84 B F H H H CH

A 'R'-CH ₃ , V-0

Comp.Nr Q _a X Y Z Z ' R 85 H H H H H CH 86 H H H 4-Cl H CH 87 H H H 4-CH H CH 88 H H H 4-CH H iC, H ₇ 89 H H H 4-CH ₃ H CH ₃ 0 (CH ₂ ] ₂ O (CHp) p 90 H H H 4-CpH, H CH 91 H H H 4-C ₂ H ₅ H CH ₃ 0 (CH ₂ ) ₂ O (CHp) p 92 H H H 4-C, H ₇ H CH 93 H H H 4-CH, 0 H CH 94 H F H 4-Cl H CH 95 H F H 4-CH H CH 96 H F H 4-C ₂ H ₅ H CH 97 H F H 4-C, H ₇ H CH 98 H Cl H 4-Cl H CH 99 H Cl H 4-CH H CH 100 H CH H 4-Cl H CH 101 H CH H 4-CH H CH

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Comp.Nr Q _a X Y Z Z ' R 102 H CH ₃ H 4-C _P H ₅ H ch ₃ 103 H H H 4-CH ₃ H CCI ₃ CHp, 104 H H H 4-C ₂ H ₅ H CCI ₃ CH ₂

Table 2

Characterization data

Com.Nr Mp ° C Comp.Nr. Mp ° C Comp. Nr. Mp ° C 1 oil 35 109-111 69 glassy 2 74-76 36 oil 70 consistent syrup 3 oil 37 oil 71 consistent syrup 4 84-87 38 oil 72 syrup 5 oil 33 oil 73 syrup 6 oil 40 oil 74 liquid in the heart

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Com.Nr Mp ° C Comp.Nr. Mp ° C Comp. Nr. Mp ° C 7 oil 41 oil 75 consistent yellow liquid 8 86-88 42 oil 76 110-112 9 86-88 43 oil 77 123-125 10 103-105 44 oil 78 syrup 11 94-96 45 oil 79 oil 12 74-76 46 oil 80 oil 13 oil 47 gel 81 83-95 14 oil 48 98-101 82 oil 15 oil 49 oil 83 oil 16 89-92 50 yellow liquid 84 118- 119.5 17 oil 51 yellow liquid 85 oil 18 97-89 52 yellow syrup 86 oil 19 89-92 53 oil 87 52-54 20 80-82 54 syrup 88 oil 21 68-70 55 orange oil 89 oil 22 oil 56 yellow oil 90 oil 2. 3 131-133 57 gel 91 oil 24 oil 58 yellow oil 92 75-78 25 83-86 59 yellow oil 93 oil 26 141-143 60 orange oil 94 oil 27 110-112 61 syrup 95 oil 28 102-103 62 yellow liquid 96 oil 29 113-115 63 syrup 97 oil 30 73-76 64 oil 98 oil 31 oil 65 syrup 99 oil 32 81-83 66 syrup 100 oil 33 oil 67 syrup 101 oil 34 116-118 68 syrup 102 oil 103 oil 104 oil

RO 114254 Bl

Many of the compounds of the invention are prepared by the following reaction.

365

370

According to the reaction, a suitably substituted methyl 2- (chloromethylphenoxy) alkanoate and a suitably substituted 4-heterocyclic phenol are heated in Ν, Ν-dimethylformamide at 80 ° C in the presence of at least one molar equivalent of potassium carbonate. . Usually the reaction occurs overnight. The preparation of the corresponding acid (R = H) is carried out by hydrolysis of the ester with aqueous sodium hydroxide and then acidifying the product with hydrochloric acid. For those compounds in which R is 2- (2-methoxyethoxyethylethyl), transenterification of the methyl ester with 2- (2-methoxyethoxyethanol) is used in the presence of titanium (IV) isopropoxy.

The intermediaries are prepared according to the following scheme:

Scheme A

375

380

385

♦ fyCHCOjR br R - (CHj) K ₂ CO _{3 r} 2-butanone Δ 17 hours (IV) 1. NaOCHj 2. NaBH < 0-5 ° C CH ₃ OH (V) SOCIj pyridine ---- ► UH ₂ CI ₂ Δ

^Z K Î ¹ λ. A— O-CHCOjR (IV) ^S CHO K > 0 & Ί o-chco ₂ r z ' (V) ^ CHjOH K G _k î ^1_ o-chco ₂ r z ' (N) ^ CHjCI

390

395

400

Thus, a mixture of suitably substituted phenyl substituted formyl and methyl-2-bromalcanoate is heated to 70 ° C in 2-butanone in the presence of potassium carbonate. Typically, the reaction occurs overnight, producing corresponding 2- (formylphenoxyisubstituted) alkanoate (IV). This compound is then reduced with sodium methoxide and sodium borohydride in methanol, giving the corresponding 2- (hydroxymethyl-phenoxy) alkanoate (IV). Reaction of compound (V) with thionyl chloride in methylene chloride in the presence of a catalytic amount of pyridine produces 2- (chloromethylphenoxy) alkanoate

405 (II) accordingly.

RO 114254 Bl

Scheme B

X anyway (Fsau Cl) (VI) ♦ o II CHjCCOjH (vn) * (PhO) jP (O) N, (vm) ♦

CHCIFj

1-methyl-2-pyrolldone (IX) ♦ ^H »“ 7¾-► ethanol

1. HjSO, _ _t 15-20 ° C ^N1N0 > · ^CuS ° ·

EtOH / hjo

EtjN toluene

To prepare the compounds of the invention, wherein Q is 4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H) -on-1-yl, 3-halo-4 is treated. -fluoro-nitrobenzene with hydrazine in isopropanol at reflux, preparing the appropriate 2-halo-4-nitrophenylhydrazine (VI). The reaction of compound (VI) with pyruvic acid in ethanol and water produces pyruvic acid (VII) 2-halo-4nitrophenylhydrazone. Preparation of the triazoline cycle is carried out by heating (VII) with diphenylphosphoryl azide and triethylamine in toluene at reflux, yielding 1- (2-halo-4-nitrophenyl) -4,5-dihydro-3-methyl-1,2,4-triazole-5 (1H) -one (VIII). Chlordifluoromethane then reacts with compound (VIII) and potassium carbonate in 1-methyl-2-pyrrolidine by heating the mixture to 120 ° C, producing 1- (2-halo-4-nitrophenyl) -4-difluoromethyl-3-methyl ~

1.2.4- triazol-5 (1H] -one (IX) Hydrogenation of (IX) in ethanol using platinum oxide as a catalyst produces 1- (4-amino-2-halophenyl) -4,5-dihydro- 4-difluoromethyl-3-methyl-

1.2.4-triazol-5 (1H) -one (X). Preparation of the intermediate (lilac) is completed by treating compound (X) with sodium nitrite in sulfuric acid and then with benzene (II) sulphate in the presence of iron (II) sulphate in a mixture of water and xylenes.

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Scheme C

In order to prepare the tetrahydrophthalimide-substituted intermediate, (IIIb) is appropriately substituted 4-aminophenol substituted with tertrahydrophilic anhydride, producing the corresponding N- (phenyl-4-hydroxy substituted) tetrahydrophthalimide.

Scheme D

(xv) (XIV)

A suitably substituted 4-nitrophenol is heated with methyl iodide, in the presence of potassium carbonate, in 2-butanone to prepare the corresponding substituted 4-nitroanisole (XI). Compound (XI) is hydrogenated on platinum oxide, producing substituted 4-methoxyaniline (XIII). The reaction of the compound (XII) with trichloromethyl chloroformate gives the corresponding substituted 4-methoxyphenyl isocyanate (XIII).

The reaction of this isocyanate with ethyl ester of glycine hydrochloride and triethylamine in chloroform gives N- (substituted phenyl-4-methoxy) -N'-ethoxy-carbonyl-methylurea (XIV). Then (XIV)

RO 114254 Bl reacts with sodium hydride and then with 2-iodine propane, eventually giving 1- (1-methylethyl) -3- (phenyl-4-methoxy-substituted) imidazodine-2,4-dione (XV). Cleavage of the methoxy group (XV) with boron tribromide gives the intermediate (s).

Scheme E

X (Xvn) / p (ra), Ho_n_ '' CHjCOjH

An appropriately substituted isocyanate phenol (Xlllb) is prepared through the first three steps of Scheme □ and then reacts with trimethylsilyl azide, to prepare suitably substituted phenyl substituted tetrazolinone. After this tetrazolinone is alkylated at position 4 with 1-bromo-3-fluorpropane to prepare the 3-fluorpropyl (XVII) substituted compound, the 4-fluorobenzyl protecting group is removed with 49% hydrobromic acid in acetic acid, giving the desired intermediate. substituted in hydroxy (XVIII).

Scheme F

SnCl ₂

NHNH,

1. HCI / NaNO

(M)

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560

The diazonium salt of 2-fluoro-4-methoxyyaniline is prepared using sodium nitrite and hydrochloric acid and then reduced "in place" with tin (II) chloride to prepare the suitably substituted phenylhydrazine. The reaction of this hydrazine with ethyl 2 cyclohexanoncarboxylate and then heating the product, in the presence of acetic acid, produces a mixture of 2- (2-fluoro-4-methoxyphenyl) -4,5,6,7-tetrahydro-1H-indazol-3-one ( XX) and 2-fluoro-4-methoxyphenyl-hydrazone of 2-cyclohexane carboxylic acid. This mixture is heated in phosphorus oxychloride, giving 3-chloro-2- (2-fluoro-4-methoxyphenyl) 4,5,6,7-tetrahydroindazole (XXI), which is then cleaved with boron tribromide to 3-chloro-2 - (2-Fluoro-4-hydroxyphenyl) -4,5,6,7-tetrahydroxyindazole (XXII) desired.

565

Scheme G

F

K ₂ CO ₃ (CHJjCO (CH ₃ ) ₂ CHI

570 (XI b)

Fe / HgO CH ₃ CO ₂ H

(ΧΠ b)

575

580

CH ₂ (CO ₂ H) ₂ + h ₂ n-co ₂ c ₂ h ₃ (xn b) + (xxm)

LITTLE ₃ IJ

---- ► CH ₂ (CNHCC ₂ C ₂ H _j ) ₂ (xxm)

585 (XXIV),, HSCH ₂ CO ₂ H (XXV)>

10% NaOH (aq.) Tetrad id rof u ran

. . NaH / CHl (XXVI) ------- ^L dimethylformamide

(Xxvn)

590

595

600. . conc. H ₂ SO ₄ (xxvn) ------—-

605 (xxvm)

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The esterification of 3-fluoro-4-nitrophenol with isopropyl iodide, in the presence of potassium carbonate, produces 2-fluoro-4-isopropoxynitrobenzene (XI b), which is reduced to 2-fluoro-4-isopropoxyaniline (XII b) with iron. in aqueous acetic acid. Malonic acid reacts with urethane (ethyl carbonate) in phosphorus oxychloride to produce malonildiurethane (XXIII) reaction (XII b) and (XXIII) is carried out with sodium nitrite and hydrochloric acid producing 2- (4-isopropoxy-2-fluorophenyl) ) hydrazonmalonildiurethane (XXIV), which is cyclized with sodium hydroxide to the corresponding 2- (phenyl substituted, 2,4-triazine-3,5-dion-6-carboxylic acid (XXV). By de-cararboxylation (XXV) with thioglycolic acid and resulting heat (XXVI) which is then methylated at position (4) with sodium hydride and methyl iodide producing 2- (substituted phenyl) -1,2,4-triazine-3,5-dione (XXVII). the isopropyl protecting groups are cleaved from the molecule with concentrated sulfuric acid, producing the desired hydroxy-substituted intermediate (XXVIII).

Scheme H

(*)

The preparation of the mercapto analogue, intermediate (III a), starts with intermediate (X), which is converted into the corresponding diazonium salt.This diazonium compound immediately reacts with copper chloride (XI) and sulfur dioxide in aqueous acetic acid, producing Properly substituted phenylsulfonyl chloride (XXIX), reduction of the sulfonyl chloride radical to the thiol group is carried out using tin (II) chloride in acetic acid, resulting in, for example, 4- (4-diflormethyl-4,3-dihydro-

3-methyl-1,2,4-triazol-5 (1H) -on-1-yl) -3-fluortiophenol (XXX), the desired intermediate.

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655

Scheme I

660

665

670

675

680

In contrast to the preparation of the other substituted heterocyclic herbicidal compounds of this invention, where the final step is the reaction between (I) and (II) to form the herbicide, in the preparation of compounds wherein Q is S-thio-1,6-diazaicyclo / 4, 3,0 / nonan-7-on-9-elimination, (II) and (III) react first to form an intermediate before heterocyclic formation. Thus, (II) reacts with 3-fluoro-4-nitrophenol in Ν, dimethylformamide in the presence of potassium carbonate, resulting in a 2- (4-nitrophenoxymethylphenoxyjalcanate (XXXI). Reduction of the compound (XXXI) with iron and water in acetic acid produces the compound corresponding amino (XXXII), which is then converted to isothiocyanate (XXXIII) with thiophosene and trimethylamine. The perhydropyridazine monohydrate and compound (XXXIII) then react, forming a 2- (4-perhydropyridazine-1-ylcarocarbonylaminophenoxymenophenylenophenoxy). (XXXIV) using trichloromethyl chloride and triethylamine gives, for example, 2- / 2- / 4- (8-thia-1,6-diazabibyclo / 4,3,0 / nonal-7-on-9-ylimino) -3 -fluorophenoxymethyl / -5-fluorophenoxymethyl / -5-methylphenoxy / methyl propionate (XXXV), the desired herbicidal compound.

685

690

695

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Similarly, compounds wherein Q is 1-methyl-trifluoromethyl-2,4-pyrimidindion3-yl can be prepared by the method of Scheme I, by the preparation thereof (XXXII). Then (XXXII) is converted to phosgene isocyanate instead of thiophosgene, and the isocyanate reacts with ethyl-3-amino-4,4,4-trifluoro-2-butenoate to give the desired herbicidal compound.

The methods for preparing the new herbicidal compounds of this invention are illustrated below. All NMR spectra are reported as protons in ppm in CDCIg.

Example 1. 2-f2- [4-f4-d7f / uormet / 7-4,5-d / 'h / dro-3-met // - 1,2,4-triazol-5 [1 H] -on Methyl -1yl) -3-fluorophenoxymethyl] -5-methylphenoxy] -propionate. (Compound 12)

Step A: Pyruvic acid 2-fluoro-4-nitrophenylhydrazone. A mixture of 21.6 g (0.126 moles) of wet 2-fluoro-4-nitrophenyl hydrazine in 1OO ml of ethanol and 11.27 g (0.128 mol) of pyruvic acid in 20 ml of water, is mixed. The reaction mixture is stirred for 20 minutes, filtered to give 15.5 g of a yellow solid, m.p. 210 ° C (decomposed) .A NMR spectrum of the product matches the structure of 2-fluoro-4-nitrophenylhydrazone. pyruvic acid: This reaction is repeated to obtain additional products.

Step B: 1- (2-Fluoro-4-nitrophenyl] -4,5-dihydro-3-methyl-1,2,4-triazol-5 (1 H) -one. 29.62 g (0.123) mixture. mol) of pyruvic acid 2-fluoro-4-nitrophenyl hydrazone, 12.45 g (0.123 mol) of triethylamine and 33.85 g (0.123 mol) of diphenylphosphoryl azide in 200 ml of toluene, is slightly heated to reflux. The heating under continuous reflux for 2 hours during which this yellow mixture becomes an orange solution After cooling to room temperature, the mixture is extracted with a solution of 17.0 g (0.425 moles) of sodium hydroxide in 200 ml. The aqueous extract is separated and is almost completely neutralized with concentrated hydrochloric acid. Even before reaching pH = 7, dry ice is added to the solution, completing the neutralization and precipitating a brown solid. Filtration of this mixture gives 26, 15 g of 1- (2-fluoro-4-nitrophenyl) -4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H] -one as a brown solid, m.p. 212 ° C. Spectrum The MRI agrees with the proposed structure.

Step C: 1- (2-Fluoro-4-nitrophenyl] -4-difluoromethyl-4,5-dihydro-1,2,4-triazol-5 (1H) one. A mixture of 5.0 g (25 mmol ) of 1- (2-fluoro-4-nitrophenyl) -4,5-dihydro-3-methyl 1,2,4-triazol-5 (1H] -one and 29.0 g (210 mmol] of potassium carbonate dried, ground in 200 ml of 1-methyl-2-pyrrolidone, heated at 120 ° C for 30 min. Chlordifluoromethane was bubbled in the reaction mixture for 5 min. Thin layer chromatography of the reaction mixture showed that the reaction was not terminated, so chlordifluoromethane is bubbled into the reaction mixture for an additional 3 minutes. The reaction mixture is poured onto ice and then neutralized with concentrated hydrochloric acid. This mixture is extracted twice with diethyl ether. wash with water, dry over anhydrous magnesium sulfate, and filter.The filtrate is evaporated under reduced pressure, leaving a dark brown solid residue.This solid is dissolved in 100 ml of acetic acid and 5 ml of acid hydrochloric, and the solution is heated to reflux for one hour. This mixture is poured over ice and then extracted with ethyl acetate. This extract is washed twice with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate is evaporated under reduced pressure,

RO 114254 Bl leaving a black oil as residue. This residue is placed on a silica gel column and eluted with methylene chloride / ethyl acetate [97,4: 2,5]. After the fractions containing the product were combined, the solvents were evaporated under reduced pressure, leaving 4.6 g of 1- (2-fluoro-4-nitrophenyl] -4-difluoromethyl, 5-dihydro-3-methyl-1,2,4- triazole-5 (1H] -one as a residue, m.p. 72-77 ° C. The NMR spectrum agrees with the proposed structure 745.

The reaction is repeated to obtain 1- (2-fluoro-4-nitrophenyl] -4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H) -one for the remainder of the synthesis.

Step D: 1- [2-Fluoro-4-aminophenyl] -4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol5 [1H) -one. A mixture of 24.5 g (85 mmol) of 1- (2-fluoro-4-nitrophenyl) -4-difluoromethyl-750

4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H) -one and 0.3 g platinum oxide in 250 ml of absolute ethanol are hydrogenated in a hydrogenation apparatus. Parr. The amount of calculated hydrogen required is taken in 45 minutes. The reaction mixture was filtered through a Buchner funnel, and the filtrate was evaporated under reduced pressure, leaving a brown solid residue darkened. The residue was placed on a silica gel column and eluted 755 with methylene chloride / ethyl acetate (75:25). After the fractions containing the product are combined, evaporation of the solvents under reduced pressure gives 20.1 g of 1- (2-fluoro-4-aminophenyl) -4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4- triazol-5 (1H) -one. The NMR spectrum agrees with the proposed structure.

Step E: 1- [2-Fluoro-4-hydroxyphenyl] -4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-7 60 5 (1H) -one. □ 20.0 g (77.4 mmol) solution of 1- (2-fluoro-4-aminophenyl] -4-difluoromethyl-

4.5- dihydro-3-methyl-1,2,4-triazol-5 (1H] -one in 100 ml of concentrated sulfuric acid is cooled to 15-20 ° C. A solution of 5.3 g (77.4 mmol] of sodium nitrite in 20 ml of water, add slowly to the solution of sulfuric acid, while the temperature is kept between 15 ° C and 20 ° C. The dark orange solution is stirred for one hour, at the same 7 65 The solution is then rapidly added to a solution of 250 g (1 mol] of copper sulphate (II) pentahydrate and 2.0 g (7.2 mmol] of iron sulphate (II) heptahydrate, in 250 ml of water. and 250 ml of mixed xylene. This two-phase solution is heated under reflux for one hour, then cooled and the phases are separated. The organic layer is dried over anhydrous sodium sulfate and filtered. The filtrate is evaporated under reduced pressure, leaving 770. a brown oil. The aqueous layer is extracted with ethyl acetate, dried over anhydrous magnesium sulfate and filtered. The extract is combined with the brown oil in the gold phase. The solvent was evaporated under reduced pressure, again leaving a brown oil. This brown oil is placed on the silica gel column and eluted with methylene chloride / ethyl acetate (90:10). The product containing fractions were combined, and the 775 solvent was evaporated under reduced pressure, leaving 12.17 g of 1- (2-fluoro-4-hydroxyphenyl) -

4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1 H / one, m.p. 112-114 ° C. The NMR spectrum consists of the structure produced.

Step F: Methyl 2- (formyl-5-methylphenoxy) propionate. A mixture of 6.0 g (44.1 mmol) of 4-methylsalicylaldehyde, 7.31 g (52.9 mmol] of potassium carbonate, 780 and 8.02 g (52.9 mmol) of 2-bromopropionate methyl, in 50 ml of 2-butanone, is heated to 70 ° C for about 17 h. The mixture is then filtered and the filtrate is evaporated under reduced pressure, leaving a residual light yellow oil.

RO 114254 Bl is placed on the column with silica gel and eluted first with diethyl ether / petroleum ether (25:75) and then with diethyl ether. After the fractions containing the product are combined and the solvents evaporate under reduced pressure, 8.2 g of methyl 2- (2formyl-5-methylphenoxy) propionate are recovered as a white solid, m.p. 6569 ° C. NMR and IR spectra confirm the proposed structure.

Step G: Methyl 2- (2-hydroxymethyl-5-methylphenoxy) -propionate. To a solution of 7.89 g (35.5 mmol) of methyl 2- (2-formyl-5-methylphenoxy) -propionate in 20 ml of methanol, cooled to 5 ° C, add a solution of D, 1 g (1.8 mmol) of sodium methoxide in 20 ml of methanol. while the temperature is maintained between □ ° C and 5 ° C, 0.3 g (9.4 mmol) of sodium borohydride and added to the reaction over a period of 10 min. The reaction mixture is allowed to warm to room temperature, where it is stirred for 2 hours. At the end of this period, the reaction mixture is poured into 75 ml of 0.25 N hydrochloric acid. This mixture is extracted twice with chloride. of methylene. The combined extracts were washed with a saturated solution of sodium chloride, dried over magnesium sulfate, and filtered. The filtrate is evaporated under reduced pressure, leaving a colorless oil as a residue. This oil is placed on a column with silica gel and eluted first with methylene chloride / ethyl acetate (95/5) and then with the same solution (90/10). After the fractions containing the product are combined and the solvents evaporated under reduced pressure, 5.76 g of methyl 2- (2-hydroxymethyl-5-methylphenoxy) methyl propionate is isolated as a colorless oil. The NMR and IR spectra confirm the proposed structure.

Step H: Methyl 2- (2-hydroxymethyl-5-methylphenoxy) -propionate. 0 solution of 2,2 g (9.8 mmol) 2- (2-hydroxymethyl-5-methylphenoxy) -propionate of methyl in 10 ml of dried methylene chloride is added to a colorless solution of 1.28 g (10, 8 mmol) of thionyl chloride together with 5 drops of pyridine in 10 ml of dried methylene chloride over a period of 10 min. This mixture was heated at reflux for one hour and then poured into 50 ml of water. The phases are separated, and the aqueous phase is extracted three times with methylene chloride. These extracts are combined with the organic phase, which is washed three times with a saturated aqueous sodium bicarbonate solution and once with a saturated aqueous sodium chloride solution. The organic phase is dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure, leaving a yellow oil as a residue. This oil is placed on a column with silica gel and eluted with methylene chloride. After the fractions containing the product are combined and the solvent is evaporated under reduced pressure, 2.06 of methyl 2- (2-hydroxymethyl-5-methylphenoxyJpropionate is recovered as a colorless oil.) The NMR spectrum agrees with the proposed structure.

Step 1: 2 [-2- [4- (4-difluoromethyl-4,5-dihydro-3-methyl-7,2,4-triazol-5- (1H] -on-1-IIJ-3-fluorophenoxymethyl] - Methyl 5-methylphenoxy] -propionate A mixture of 0.5 g (1.9 mmol) of 1- (2-fluoro-4-hydroxyphenyl] -4-difluoromethyl-4,5-dihydro-3-methyl-1 , 2,4-triazol-5 (1H) -one, 0.39 g (2.8 mmol) of anhydrous potassium carbonate and 0.92 g (3.8 mmol) of 2- [2-hydroxymethyl-5-methylphenoxy ] -methyl propionate in 20 ml of Ν, Ν-dimethylformamide is heated to 90 ° C for about 17 hours. At the end of this period the mixture is poured over ice, and the resulting mixture is extracted with ethyl acetate.

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The extract was washed with water, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure, leaving an orange oil as a residue. This oil is placed on a silica gel column and eluted first with methylene chloride and then with methylene chloride / ethyl acetate (97.5 / 2.5). After the fractions containing the product are combined and the solvents evaporated under reduced pressure, O, 82g of 2 [-2- [4- (4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-) is recovered. triazol-5- (1H) -on-1-yl) -3-fluorophenoxymethyl) -5-methylphenoxy] -propionate as a yellow oil. The NMR and IR spectra confirm the proposed structure. NMR: 1.60 (d, 3H, J _HH = 8.0 Hz); 2.30 (s, 3H); 2.44 (s, 3H); 3.76 (s, 3H); 4.84 (q, 1H, J _HH = 8.0 Hz); 5.16 (dd, 2H, J _HH = 10.0 Hz); 6.56 (s, 1H); 6.78-7.32 (m, 6H).

Example 2 Methyl 2- [2 - [- fluoro-4- (3,4,5, 6-tetrahydro-1-phthalimidyljphenoxymethyl] -5-chlorophenoxypipropionate. (Compound 27}

Step A: Synthesis of 4-amino-3-fluorophenol. To a mixture of 10 g (64 mmol) of 3-fluoro-4-nitrophenol in 10D ml of acetic acid and 10 ml of water, heated to 50 ° C, add 10 g (179 mmol) of iron powder to small portions during a period of 35 min. The stirred reaction mixture was heated to 50 ° C for 3 h, then cooled and filtered. The filtrate is used in Stage B without further purification.

Step B: N- (2-fluoro-4-hydroxyphenyl] -3,4,5,6-tetrahydrophthalimide. The filtrate from Step A is mixed with 9.74 g (64 mmol) of anhydride 3,4,5,6-. tetrahydrophthalic, and the mixture is heated to reflux for about 64 h. At the end of this period, the dark brown solution is poured onto ice and extracted successively with ethyl acetate and diethyl ether. The extracts are combined, washed with water, dry over anhydrous magnesium sulfate and filter. The solvent is evaporated under reduced pressure from the filtrate, leaving a dark brown oil as the filtrate. It is placed on a column with silica gel and eluted with methylene chloride / ethyl acetate (95 / 5) After the fractions containing the product are combined and the solvents evaporated under reduced pressure, 14.71 g of N- (2-fluoro-4-hydroxyphenyl-3,4,5,6-tetrahydrophthalimide is recovered as an orange solid, mp 132-136 ° C. The NMR spectrum confirms the proposed structure.

Step C: Methyl-2- (5-chloro-2-formylphenoxy) -propionate. A mixture of 22 g (141 mmol) of 4-chloroacylaldehyde, 30 g (220 mmol) of anhydrous potassium carbonate and 39 g (184 mmol) of methyl 2-brompropionate in 120 ml of N, N-dimethylformamide are heated to 80 ° C for about 17 h. At the end of this period, the reaction mixture is poured over ice and extracted successively with diethyl ether and ethyl acetate. The combined extracts are washed with water, dried over anhydrous magnesium sulfate and filtered. The solvents are evaporated under reduced pressure, leaving a residue weighing 20 g. This residue is purified by placing it on the silica gel column and eluting with diethyl ether / petroleum ether (25/75). After the fractions containing the product are combined and the solvents were evaporated under reduced pressure, 0.23 g of methyl propionate [5-chloro-2-formylphenoxy] was isolated as a yellow liquid, similarly the other fractions were combined and evaporated to give 1.69 g of 2- (3-Chloro-2-formylphenoxy] -propionate by me Til in the form of a yellow liquid The NMR spectra of the two compounds are in agreement with the product structures of each. This reaction is repeated several times.

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Step D: Methyl 2- (5-chloro-2-hydroxymethylphenoxy) -propionate. To a solution of 0.1 g (18 mmol) of sodium methoxide in 20 ml of methanol which is cooled to 5 ° C, add a solution of 8.0 g of 2- (5-chloro-2-formylphenoxy) -methyl propionate in 200 ml of methanol, while the temperature is maintained between 0 ° C and 5 ° C, to this mixture is added 0.5 g (13 mmol) of sodium boride hydride. This solution is allowed to warm to room temperature, where it is stirred for 4 hours. At the end of this period the reaction mixture is poured into 100 ml of 0.25 N hydrochloric acid. This mixture is extracted. with methylene chloride. The extract is washed with a saturated aqueous solution of sodium chloride. It is dried over anhydrous magnesium sulfate, and filtered. The filtrate is evaporated under reduced pressure, leaving a yellow oil as a residue. This oil is placed on a silica gel column and eluted with methylene chloride / ethyl acetate (95/5). the product containing rations are combined and the solvents evaporated under reduced pressure, 4.42 g of methyl 2- (5-chloro-2-hydroxymethylphenoxy] -propionate is isolated as an orange oil, which is then solidified with a point of mp 51-52 ° C.

Step E: Methyl 2- (2-chloromethyl-5-chlorophenyl) -propionate. By the method of Example (1), step H, 1.0 g (3.8 mmol) of methyl 2- (5-chloro-2-hydroxymethylphenoxy) -propionate and 0.5 g (4.2 mmol) of chloride of thionyl is reacted with 20 ml of methylene chloride. After purification 0.88 g of methyl 2-chloromethyl-5-chlorophenoxy) -propionate is isolated as a yellow liquid. The NMR spectrum confirms the structure.

Step F: Methyl 2 - [- 2 [-3-fluoro-4- [3,4,5,6-tetrahydro-1-phthalimidyl) phenoxymethyl] -5-chlorophenoxy} propionate.

By the method of Example (1), step I, 0.5 g (1.9 mmol) of N- (2-fluoro-4-hydroxyphenyl] -3,4,5,6-tetrahydrophthalimide, 0.88 g (9.4 mmol) of methyl 2- (2-chloromethyl-5-chlorophenoxy] -propionate and 0.39 g (2.8 mmol] of potassium carbonate are reacted in 200 ml of 2-butanone. After purification, 0.58 g of 2 is isolated. Methyl - / - 2/3-fluoro-4- / 3,4,5,6-tetrahydro-1-phthalimidyl) phenoxymethyl / -5-chlorophenoxy / -5-propionate is isolated as a yellow solid with a melting point 110-. 112 ° C. NMR and IR spectra confirm the proposed structure. NMR: 1.64 (d, 3H, J _HH = 8 Hz); 1.80 (bs, 4H); 2.40 (bs, 4H); 3.78 (s, 3H); 4.84 (q, 1H, J _HH = 8 Hz); 5.14 (s, 2H); 6.78-7.38 (m, 6H).

Example 3. 2 - [- 2 [-3-fluoro-4- [1- (1-methylethyl) -imidazolidin-2,4-dion-3-yl] phenoxymethyl) -

Methyl 5-chlorophenoxy] -propionate. (Compound 44)

Step A: 2-Fluoro-4-methoxyphenyl isocyanate. To a solution of 13.75 g (96.7 mmol) of 2-fluoro-4-methoxyyaniline in 120 ml of toluene, slowly add a solution of 19.13 g (96.7 mmol] of trichloromethyl chloroformate for 30 minutes. in 30 ml of toluene. During the addition the temperature rises to 35 ° C. The reaction mixture is stirred without external heating for 30 minutes and then heated at reflux for about 17 h. At the end of this period the solvent is removed. by distillation, leaving 2-fluoro-4-methoxyphenyl isocyanate as a purple liquid, which is immediately used in step B.

Step B: N- (2-Fluoro-4-methoxyphenyl) -N'-ethoxycarbonylmethylurea. A 2-fluoro-4-methoxyphenyl isocyanate solution, which has 16.2 g (96.7 mmol) of step A, 13.5 g

RO 114254 Bl

915 (96.7 mmol) of glycine ethyl ester hydrochloride in 100 ml of chloroform is placed in a vessel, and a solution of 9.28 g (96.7 mmol) of triethylamine in 25 ml of chloroform is added to a period of 20 min. during the addition the temperature rises to 38 ° C. After the addition is complete, the reaction mixture is stirred at room temperature for three hours and then poured into a mixture of heptane and water. By filtration, N- (2-fluoro-4-methoxyphenyl) -N'-ethoxycarbonylmethylurea is isolated from this mixture as a purple solid with a mp 158-159 ° C. The organic phase of the filtrate was separated, dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated from the filtrate under reduced pressure, leaving a residue of a purple solid. This solid is recrystallized from ethyl acetate / petroleum ether. The recrystallized solid is placed on a silica gel column and eluted successively with methylene chloride, methylene chloride / ethyl acetate (90/10) and finally methylene chloride / ethyl acetate (75/25). After the fractions containing the product are combined and the solvents evaporated under reduced pressure, additional N- (2-fluoro-4-methoxyphenyl) -N'-ethoxycarbonyl-methylurea is isolated as a purple solid with a mp 158-159 °. C. The total yield of N- (2-fluoro-4-methoxyphenyl) -N'-ethoxycarbonyl-methylurea is 17.33 g. The NMR spectra of these solids confirm the proposed structure.

Step C: 1- (1-Methylethyl] -3- [2-fluoro-4-methoxyphenyl) -imidazolin-2,4-dione.

A solution of 17.02 g (63 mmol) of, N- (2-fluoro-4-methoxyphenyl) -N'-ethoxy-carbonylmethylurea in 50 ml of Ν, Ν-dimethylformamide is added dropwise to a suspension of 2, 65 g (66.2 mmol) of sodium hydride in 30 ml of Ν, Ν-dimethylformamide, over a period of 20 min. The gas release and a slight increase in temperature occur during the addition. This mixture is stirred at room temperature for 45 minutes, during which time it becomes a homogeneous solution. To this solution, a solution of 21.42 g (126 mmol) of 2-iodopropane and 10 ml of Ν, Ν-dimethylformamide is added dropwise over a period of 15 minutes. The temperature increases to 38 ° C during the The reaction mixture is stirred for about 65 hours, then ice is poured off and extracted with diethyl ether. The extracts are washed twice with water, dried over anhydrous magnesium sulfate, and filtered. reduced pressure, leaving an orange oil as a residue. This oil is placed on a column with silica gel and eluted successively with mixtures of (97.5 / 2.5) and (95/5) of methylene chloride and ethyl acetate. After the fractions containing the product are combined and the solvents evaporated under reduced pressure, 585 g of 1- (1-methylethyl-3- (2-fluoro-4-methoxyphenyl) imidazoldin-2,4-dione is isolated as a orange solid with mp 8890 ° C.

Step D: 1- (1-Methylethyl-3- (2-fluoro-4-meth; oxyphenyl] -imidazoldin-2,4-dione.

□ 1M solution of boron tribromide in 41.6 ml (41.6 mmol) of methylene chloride is cooled to -20 ° C. while maintaining this temperature, a solution of 5.35 g (20.8 mmol) of 1- (1-methylethyl-3- (2-fluoro-4-methoxyphenyl) -imidazoldin-2,4-dione in 25 ml of methylene chloride is added to the reaction over a period of eight minutes. The reaction mixture is allowed to warm to room temperature, where it is stirred for about 17 hours. At the end of this period, the reaction mixture is poured onto the reaction mixture.

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RO 114254 Blast ice, and the resulting two-phase mixture is filtered. The organic phase was separated, dried over anhydrous magnesium sulfate, and filtered, the filtrate was evaporated under reduced pressure, leaving a black solid as a residue. This solid is recrystallized from ethyl acetate / petroleum ether to give 3.25 g of 1- (1-methylethyl-3- (2-fluoro-4-methoxyphenyl] imidazoldin-2,4-dione, a solid of the color of the bronze with melting point 190-192 ° C. The NMR and IP spectra agree with the proposed structure.

Step E: Methyl 2- [2- [3-fluoro-4- [1- (1-methylethyl) -imidazoldin-2,4-dione-3-yl] -phenoxymethyl] -5-chlorophenoxypropionate. By the method of Example (1), step I, 0.6 g (2.4 mmol) of 1- (1-methylethyl-3- (2-fluoro-4-methoxyphenyl) -imidazoldin-2,4-dione, 1 , 24 g (4.8 mmol) of 2- (2-chloromethyl-5-chlorophenoxy) -methyl propionate (example 2, step E) and 0.5 g (3.6 mmol) of potassium carbonate react in 25 ml of 2-butanone 1.04g methyl-2- [2- [3-fluoro-4 - H-1- (1-methylethyl) -imidazoldin-2,4-dion3-yl] phenoxymethyl] - after purification 5-chlorophenoxy] propionate - as a yellow oil - NMR and IR spectra agree with the proposed structure NMR: 1.24 (d, 6H, J _HH = 8 Hz); 1.64 (d, 3H, J _HH = 8 Hz); 3.68 (s, 3H); 3.96 (s, 1H); 4.44 (septet, 1H, J _HH = 8 Hz); 5.04 (q, 1H, J _HH = 8 Hz) ; 5.24 (s, 2H); 6.80-7.34 (m, 5H).

Example 4. 2- [2- [4- [1,4-dihydro-4- [3-fluorpropyl) -5-tetrazol-5-on-1-yl] -3-fluorophenoxy-methyl] -5-methylphenoxy] methyl propionate. [Compound 64)

Step A: 4-Fluorophenylmethyl-3-fluoro-4-nitrophenyl ether A mixture of 10 g (63 mmol) of 3-fluoro-4-nitrophenyl, 17 g (90 mmol) of fluorophenylmethyl chloride and 12.42 g (90 mmol) of potassium carbonate in 80 ml of methylethylketone, heated to 70 ° C for about 17 hours and stirred. The reaction mixture is then cooled and filtered and the filtrate is evaporated under reduced pressure leaving 13.1 g of 4-fluoromethyl-3-fluoro-4-nitrophenyl ether as a mp 90-91 ° C.

Step B: 4-Fluorophenylmethyl-4-amino-3-fluorophenyl ether. A solution of 11 g (41 mmol) of 4-fluorophenylmethyl-3-fluoro-4-nitrophenyl ether in 100 ml of glacial acetic acid and 10 ml of water is heated to 50 ° C. To this hot solution is added 10 g (180 mmol) of iron powder. The reaction mixture is allowed to cool to room temperature, where it is stirred for an additional hour. The reaction mixture is filtered through a Celite (R) filter aid layer, and the Celite layer is then washed with ethyl acetate and 200 ml of water. The washing solutions and filtrate are combined, and the organic phase is separated. The organic phase was dried over anhydrous magnesium sulfate, filtered and the solvent was evaporated under reduced pressure leaving a dark oil as a residue. This oil is placed on a silica gel column and eluted with methylene chloride. The product-containing fractions are combined and the solvent is evaporated under reduced pressure, leaving 0.8 g of 4-fluorophenylmethyl-4-amino-3-fluorophenyl ether as a mp 42-43 ° C.

Step C: 4- [4-fluorophenylmethoxy) -2-fluorophenyl isocyanate. To a solution of 6.5 g (27.6 mmol) of 4-fluorophenylmethyl-4-amino-3-fluorophenyl ether in toluene, stirred at room temperature, slowly add 3.95 g (20 mmol) of trichloromethyl chlorformate . During the addition a dense precipitate is formed. When the addition is complete, the reaction mixture is stirred for one hour at room temperature and then at reflux

RO 114254 Bl for about 17 h. Toluene is removed by distillation, leaving 7.1 g of 4- (4-fluorophenylmethoxy) -2-fluorophenyl isocyanate.

Step D: 1- [4- [4-fluorophenylmethoxy) -2-fluorophenyl] -1,4-dihydro-5H-tetrazol-5-one. A mixture of 7.1 g (27 mmol) of 4- (441 uorophenylmethoxy) -2-fluorophenyl isocyanate and 7.0 g (60 mmol) of trimethylsilyl azide is heated at reflux for about 17 hours. The solution is then left. cool to room temperature before being poured onto ice. A solid is formed which is recovered by filtration. The solid is dried, leaving 8.08 g of 1 - / 4- (4-fluorophenylmethoxy) -2-fluorophenyl / -. 1,4-dihydro-5H-tetrazole-5-one with mp 171-172 ° C.

Step E: 7- [4- {4-fluorophenylmethoxy) -2-fluorophenyl] -7,4-dihydro-4- [3-fluorpropyl) -5H-tetrazole-5-one. A mixture of 7.0 g (23 mmol) of 1- / 4- (4-fluorophenylmethoxy) -2-fluorophenyl / -1,4-dihydro-5H-tetrazole-5-one, 4.23 g (30 mmol) of 1-bromo-3-fluorpropane and 4.14 g (30 mmol) of anhydrous potassium carbonate in 60 ml of N, N-dimethylformamide is heated to 70 ° C for about 17 h. The mixture is allowed to cool to room temperature before being poured onto ice. The formed solid is filtered off and dried. This solid is then placed on a silica gel column and eluted with methylene chloride. The fractions containing the product are combined and the solvents evaporated under pressure. reduced, leaving 6.35 g of 1- / 4- (4-fluorophenylmethoxy) -2-fluoro-phenyl / -1,4-dihydro-4- (3-fluorpropyl) -5H-tetrazole-5-one with a melting point 86 -88 ° C.

Step F: 7- (2-Fluoro-4-hydroxyphenyl} - 1,4-dihydro-4- (3-fluorpropyl) -5H-tetrazole-5-one. At a solution of 5.6 g (15.3 mmol ) of 1- / 4- (4-fluorophenylmethoxy) -2-fluorophenyl / -1,4-dihydro-4- (3-fluorpropyl) -5H-tetrazol-5-one in 60 ml of glacial acetic acid, 5 ml of 49% hydrobromic acid This mixture is heated to reflux for 90 minutes, then cooled to room temperature. The reaction mixture is poured onto ice, and the resulting aqueous solution is extracted with diethyl ether. The combined extract is dried over magnesium sulfate, The mixture was filtered, and the solvent was evaporated under reduced pressure, leaving 4.35 g of 1- (2-fluoro-4-hydroxyphenyl) -1,4-dihydro-4- (3-fluoropropyl) -5H-tetrazole-5-one. as a residue.

Step G: 2- [2- [4- [1,4-dihydro-4- (3-fluorpropyl] -5H-tetrazol-5-on-7-yl] -3-fluorophenoxymethyl] -5-methylphenoxy] by the method of Example (1), step I, 0.85 g (3.3 mmol) of 1- (2-fluoro-4-hydroxyphenyl) -1,4-dihydro-4- (3-fluoropropyl) ) -5H-tetrazol-5-one and 1.21 g (5 mmol) of methyl 2- (2-chloromethyl-5-methylphenoxy) -propionate (Example 1, step H) react in the presence of 0.7 g ( 5 mmol) of anhydrous potassium carbonate in 60 ml of Ν, Ν-dimethylformamide, yielding 0.42 g of 2- (2- (4- (1,4-dihydro-4- (3-fluoropropyl) -5H-tetrazole-5) methyl -on-1-yl] -3-fluorophenoxy-methyl] -5-methylphenoxy] propionate as an oil NMR spectrum confirms the proposed structure NMR: 1.64 (d, 3H, J _HH = 8 Hz); 2.2-2.4 (m, 2H); 2.32 (s, 3H); 3.72 (s, 3H); 4.18 (t, 2H, J _HH = 8 Hz); 4.50- 4.64 (dt, 2H, J _HH = 8 Hz, J _HF = 45 Hz); 4.84 (q, 1H, J _HH = 8 Hz); 5.20 (q, 2H, J _HH = 8 Hz) ; 6.58-7.40 (m, 6H).

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Example 5. Methyl 2- [2- [4- [3-chloro-4,5,6,7-tetrahydroimidazol-2-yl) -3-fluorophenoxymethyl] 5-chlorophenoxy] -propionate. [Compound 66]

Step A: 2-Fluoro-4-methoxyphenylhydrazine. With vigorous stirring, 9.15 g (65 mmol) of 2-fluoro-4-methoxyyaniline is added to 60 ml of concentrated hydrochloric acid which is cooled to -10 ° C. A solution of 4.83 g (70 mmol) of sodium nitrite in 30 ml of water is slowly added dropwise, while the temperature is maintained at or below -10 ° C. When the addition is complete, the reaction mixture is stirred at -10 ° C for one hour, then 33.85 g (150 mmol) of tin chloride dihydrate (II) in 50 ml of concentrated hydrochloric acid is added slowly. , in drops, while the temperature is kept below -5 ° C. After the reaction mixture is stirred for one hour, while warming to room temperature, the crude product is filtered out of the mixture and dissolved in 250 ml of water. This solution is made in principle with 4N sodium hydroxide and extracted with methylene chloride. The combined extracts were dried over anhydrous sodium sulfate and filtered. The filtrate was placed on a silica gel column and eluted with methylene chloride to remove the colored impurities and then with ethyl acetate to obtain the desired product. The solvent was evaporated under reduced pressure to give 6.30 g of 2-fluoro-4-methoxyphenylhydrazine. NMR spectra confirm the proposed structure.

Step B: 2- (2-Fluoro-4-methoxyphenyl] -4,5,6,7-tetrahydro-1H-indazol-3-one. To a solution of 6.28 g (40 mmol) of 2-fluorine -4-methoxyphenylhydrazine in 200 ml of toluene, 6.82 g (40 mmol) of ethyl 2-cyclohexanone carboxylate is added after stirring, this mixture is heated under reflux under a nitrogen atmosphere, while the water is removed with a device Dean-Stark - After all the water is removed the reaction mixture is allowed to cool and the solvent is evaporated under reduced pressure, leaving a residue which is then dissolved in acetic acid.This solution is heated to reflux for approximately 16 hours, after The solvent is evaporated under reduced pressure, leaving a residue. This residue is dissolved in toluene, which is also evaporated under reduced pressure. The residue is dissolved in ethyl acetate and placed on a silica gel column and eluted with acetate. An attempt to crystallize the product by dissolving it in diethyl ether d until the ethyl acetate evaporated was not successfully crowned. After the solvent is evaporated from this product, it is re-heated to reflux in acetic acid and allowed to cool to room temperature, where the solution is stirred for 48 hours. The solvent is evaporated under reduced pressure, leaving a residue of 4, 32 g. Two further fractions weighing 0.80 g and 2.75 g are recovered by extracting the reaction mixture before the solvent is evaporated. The NMR spectrum of the residue shows that it is a mixture of 2- (2-fluoro-4-methoxyphenyl) 4,5,6,7-tetrahydro-1H-indazol-3-one and 2-fluoro-4-methoxyphenylhydrazone of 2-cyclohexanoncarboxylic acid.

Step C: 3-Chloro-2- [2-fluoro-4-methoxyphenyl) -4,5,6,7-tetrahydro-1H-indazole. 4.32 g of residue from step B, is stirred at room temperature with 5.37 g (35 mmol) of phosphorus oxychloride until complete dissolution occurs. At this point the reaction mixture is heated under reflux under nitrogen for one hour. Phosphorus oxychloride

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1080 is evaporated from the reaction mixture under reduced pressure, leaving a residue of 1.5Og. This residue, together with a similar residue of 0.30 g from a previous experiment, is placed on a silica gel column and eluted with hexane / ethyl acetate (4: 1], after the fractions containing the product are combined and the solvents are evaporated under reduced pressure, 0.50 g of 3-chloro-2- (2-fluoro-4-methoxyphenyl) -4,5,6,7-tetrahydroindazole is isolated, the NMR confirms the proposed structure.

Step D: 3-Chloro-2- (2-fluoro-4-methoxyphenyl] -4,5,6,7-tetrahydroindazole.

A 1N solution of 18 ml (18 mmol) of boron tribromide in methylene chloride is diluted with 17 ml of methylene chloride and then cooled to below -10 ° C under a nitrogen atmosphere. A solution of 3-chloro-2- (2-fluoro-4-methoxyphenyl) -4,5,6,7-tetrahydroindazole in 25 ml of methylene chloride is added dropwise keeping the temperature below -10 ° C. After the addition is complete, the reaction mixture is allowed to warm to room temperature, which is stirred for 16 h. The mixture is then poured into ice-cold water, and the resulting mixture is stirred for 30 minutes. The mixture is filtered and the filtrate is passed through a short column of silica gel. The organic phase was separated, dried over anhydrous sodium sulfate, and filtered. The solvent was evaporated from the filtrate under reduced pressure, leaving 0.60 g of 3-chloro-2- (2-fluoro-4-methoxyphenylJ4,5,6,7-tetrahydroindazole as an off-white solid with m.p. 214216 ° C. The NMR and IR spectra agree with the proposed structure.

Step E: Methyl 2- [2- [4- (3-chloro-4,5,6,7-tetrahydroindazol-2-yl) -3-fluoro-phenoxymethyl] -5-chlorophenoxypropionate. By the method of Example I, step I, 0.49 g (1.6 mmol) of 3-chloro-2- (2-fluoro-4-hydroxyphenyl) -4,5,6,7-tetrahydroindazole and 0.52 g (2 mmol) of

Methyl 2- (2-chloromethyl-5-chlorophenoxy) propionate. (Example 2, step E) reacts in the presence of 0.41 g (3 mmol) of anhydrous potassium carbonate in 30 ml of Ν, Ν dimethylformamide, yielding 0.64 g of 2- / 2- / 4- (3-chloro -4,5,6,7-tetrahydro-indazol-2-yl] -

Methyl 3-fluoro-phenoxymethyl / -5-chlorophenoxy / propionate as a syrup. The NMR and IR spectra agree with the proposed structure. NMR: 1.64 (d, 3H, J _HH = 8 Hz); 1.82 (m, 4H); 2.50 (t, 2H, J _HH = 4 Hz); 2.68 (t, 2H, J _HH = 4 Hz); 3.76 (s, 3H); 4.82 (q, 1H, J _hh = 8 Hz); 5.18 (s, 2H); 6.78-7.40 (m, 6H).

Example Methyl 6.2- [2 - [- 4-methyl-1,2,4-triazin-3,5-dion-2-yl] -3-fluorophenoxymethyl] -5-methylphenoxypipropionate. (Compound 70)

Step A: 4-Isopropoxy-2-fluoraniline. A stirred vessel containing 350 ml of acetic acid is heated to 80-85 ° C in a nitrogen atmosphere. To this vessel is added

39.1 g (700 mmol) of iron powder, and this mixture is stirred for one hour. A solution of 4-isopropoxy-2-fluornitrobenzene in 250 ml is added to the mixture as droplets. Upon completion of the addition, the reaction mixture is heated to 80-85 ° C for one hour. After cooling to below 40 ° C, the mixture is filtered, and the solvent is evaporated under reduced pressure, leaving a residue. This residue is dissolved in a mixture of water and diethyl ether. The organic layer is separated and washed successively with saturated aqueous sodium bicarbonate solutions and sodium chloride. It is then dried over anhydrous magnesium sulfate, filtered through a short column of silica gel and the solvent is

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RO 114254 Bl evaporates under reduced pressure, leaving an impure residue containing significant quantities of acetamide in addition to the desired product. This residue is suspended in 500 ml of 2N hydrochloric acid for one hour. The mixture of hydrochloric acid is extracted with diethyl ether, and the two phases are separated. The aqueous sodium hydroxide solution is added to the aqueous hydrochloride solution until it becomes basic. The basic solution is extracted with diethyl ether, and the extract is dried over anhydrous magnesium sulfate and filtered. After evaporation of the solvent under reduced pressure, the residue is recrystallized from diethyl ether / petroleum ether to give 16.9 g of 4-isopropoxy-2-fluoraniline as an oil which is dark in color. The NMR spectrum agrees with the proposed structure.

Stage B: Malonildiuretum. With a mortar and pestle grind 10.4 g (100 mmol) of malonic acid and 18.0 g (210 mmol) of ethyl carbamate to a fine powder, place this powder in a bowl and add 16, 0 ml (167 mmol) of phosphorus oxychloride This mixture is heated to 80 ° C until the gas cessation ceases. After the reaction mixture is cooled to room temperature, 210 ml of water is added. When the glass mixture becomes fluid, extracts with ethyl acetate The combined extracts are washed successively with saturated aqueous solutions of sodium bicarbonate and sodium chloride and then dried over anhydrous magnesium sulfate and filtered. The solution is filtered through a short column of silica gel, which is then filtered. The solvent is then evaporated under reduced pressure, leaving a crystalline mass of malonyldiurethane weighing 10.62 g. The NMR spectra agree with the proposed structure.

Step C: 2- (4-isopropoxy-2-fluorophenyl] hydrazone-maloniidiurethane. A mixture of 5.92 g (35 mmol) of 4-isopropoxy-2-fluoraniline, 10.6 g (43 mmol) of malonylurethane and 42 , 02 g (500 mmol) of sodium acetate is suspended in 1000 ml of water with vigorous stirring, to this suspension is added 25 ml of hydrochloric acid 12 N. The reaction mixture is cooled to 10 ° C, and while this is Keep the temperature slowly added, a solution of 2.42 g (35 mmol) of sodium nitrite in 25 ml of water. The reaction mixture is allowed to warm slightly to room temperature where it is stirred under a nitrogen atmosphere for a long time. About 16 h. During this period, a yellow solid precipitates. The mixture is filtered, and the yellow solid is washed successively with water and diethyl ether. After drying, 9.2 g of 2- (4-isopropoxy-2). -fluorophenyl) -hydrazonmalonildiurethane is isolated as a yellow solid, NMR and IR spectra agree with the structure of opposite.

Step D: 2- [4-Isopropoxy-2-fluorophenyl) -1,2,4-triazine-3,5-dione-6-carboxylic acid. To a stirred solution of 8.94 g (21 mmol) of 2- (4-isopropoxy-2-fluorophenyl) -hydrazonmalonildiurethane in 125 ml of ethanol and 125 ml of tetrahydrofuran is added 75 ml (134 mmol) of aqueous potassium hydroxide. , initially forming a precipitate, which then dissolves. After this mixture was stirred for 30 minutes at room temperature, 300 ml of 11.7 N hydrochloric acid was added, stirring gently. The tetrahydrofuran is evaporated under reduced pressure, and the residue is then extracted with ethyl acetate. The combined extracts are treated with bleaching charcoal, dried over magnesium sulfate

RO 114254 Bleached anhydrous, and filtered through a short column of silica gel, which was then eluted with 116 O ethyl acetate. The solvent was evaporated from the filtrate to give 4.7 g of 2- (4-isopropoxy-2-fluorophenyl] -1,2,4-triazine-3,5-dion-6-carboxylic acid. The NMR spectra were in agreement with the proposed structure. .

Step E: 2- (4-Isopropoxy-2-fluorophenyl) -1,2,4-triazine-3,5-dione. A 4.7 g (15.2 mmol) solution of 2- (4-isopropoxy-2-fluorophenyl) -1,2,4-triazine-3,5-dion-6-carboxylic acid ii65 in 5 ml of acid mercaptoacetic is heated to 140-145 ° C for 2 hours in a nitrogen atmosphere. After this mixture is cooled, pour 150 ml of saturated aqueous sodium bicarbonate solution with vigorous stirring. To this mixture is added an equal volume of ethyl acetate, and the resulting layers are separated. The organic layer is washed twice with 150 ml of saturated aqueous sodium bicarbonate solution of ii70 sodium and once with 150 ml of saturated aqueous sodium chloride solution. The organic solution is then dried over anhydrous magnesium sulfate and filtered. The solvent is evaporated under reduced pressure, leaving a syrup that crystallizes in a yellowish-orange solid when standing. This solid is recrystallized from ethyl acetate / petroleum ether (1: 1), giving 0.6 g of 2- (4-isopropoxy-2-fluorophenyl) -1,2,4-triazine-2,5-dione under form 1175 of a yellow solid. The MRI confirms the proposed structure. This reaction is repeated to obtain additional material for the next reaction.

Step F: 2- (4-Isopropoxy-2-fluorophenyl} -4-methyl-1,2,4-triazine-3,5-dione.

A solution of 3.25 g (12.3 mmol) of 2- (4-isopropoxy-2-fluorophenyl) -1,2,4-triazine-3,5-dione in 30 ml of Ν, Ν-dimethylformamide is added to a suspension of 0.5 g (12.5 mmol) of sodium hydride in 30 ml of Ν, Ν-dimethylformamide at room temperature When the gas release ceases, 3.55 g (25 mmol) of iodomethane is added to -a portion. This mixture is stirred for one hour, without heating, then poured into 300 ml of dilute hydrochloric acid. The mixture is extracted several times with diethyl ether and the extracts are combined. The ether extract is washed successively with water and a saturated aqueous solution of sodium chloride 1185. It is then dried over anhydrous magnesium sulfate and filtered through a column of silica gel. The solvent is evaporated under reduced pressure, leaving 2.8 g of 2- (4 -isopropoxy-2-fluorophenyl) -4-methyl-1,2,4-triazine-3,5-dione as a syrup NMR spectra confirm the proposed structure.

Step G: 2- [4-hydroxy-2-fluoromethyl] -4-methyl-1,2,4-triazine-3,5-dione. Sulfuric acid 1190, concentrated, 5 ml, which is cooled to 0-5 ° C, is mixed with 0.8 g (10 mmol) of 2 (4-isopropoxy-2-fluorophenyl) -4-methyl-1,2,4- triazine-3,5-dione cooled to 0 ° C. The mixture is kept at 0 ° C for 10 minutes, during which time it becomes homogeneous. The mixture is then poured into ice water, and the resulting mixture is extracted with ethyl acetate. The extract was washed successively with a saturated aqueous sodium bicarbonate solution and an 1195 saturated aqueous sodium chloride solution. The extract was dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated from the filtrate under reduced pressure, leaving a residue. This residue is placed on the silica gel column and eluted with ethyl acetate / hexane (1: 1). After the fractions containing the product are combined and the solvents are evaporated under reduced pressure, 1.38 g of 2- (4-hydroxy-2-fluorophenyl) -4-methyl-1,2,4-1200 triazine-3,5- dions are recovered in the form of a syrup. The MRI confirms the proposed structure.

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Step H: Methyl 2- [2 - [- 4-methyl-1,2,4-triazin-3,5-dion-2-yl) -3-fluorophenoxymethyl] -5-methylphenoxypipropionate. By the method of Example 1, step I, 0.47 g (2 mmol) of 2- (4-hydroxy-2-fluorophenyl) -4-methyl-1,2,4-triazine-3,5-dione and 0.73 g (3 mmol) of methyl 2- (2-chloromethyl-5-methylphenoxy] propionate reacts in the presence of 0.41 g (3 mmol) of anhydrous potassium carbonate in 30 ml of Ν, Ν-dimethylformamide, yielding 0.70 g of Methyl 2- / 2- / - 4-methyl-1,2,4-triazine-3,5-dion-2-yl) -3-fluorophenoxymethyl / -5-methylphenoxy / propionate as a syrup. The NMR and IR spectra agree with the proposed structure. NMR 1.60 (d, 3H, J _HH = 8.0 Hz); 2.30 (s, 3H); 3.40 (s, 3H); 3.78 (s, 3H); 4.84 (q, 1H, J _HH = 8.0 Hz); 5.18 (dd, 2H, J _HH = 1O Hz); 6.58 (s, 1H); 6.8-7.3 (m, 5H); 7.54 (s, 1H).

Example 7. 2- [2 - [- 4 (4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1 H) -on-1-yl) -3-fluorophenoxymethyl] - Methyl 5-methylphenoxy-] propionate. (Compound 72)

Step A: 4- (4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H] -on-1-yl) -3-fluorophenylsulfonyl chloride. A mixture of 2.02 g (7.8 mmol) of 1- (2-fluoro-4-aminophenyl) -

4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H) -one (Example 1 step D) in 20 ml of hydrochloric acid is cooled to 0 ° C and 0, 55 g (8.4 mmol) of sodium nitrite in 5 ml of water is added slowly while the temperature is maintained at 0-5 ° C. The yellow solution is stirred at room temperature for 2 h. Meanwhile, a solution of 1.08 g (8 mmol) of copper chloride (II) in 5 ml of water and 20 ml of acetic acid and sulfur dioxide is prepared. introduced into the solution until it is saturated for ten min. After stirring for 2 hours, the yellow solution is slowly added to the solution saturated with sulfur dioxide. The mixture turns green and a yellow precipitate forms. During the addition, the temperature rises to 32 ° C. The reaction mixture was stirred for 1 hour at room temperature and then poured onto ice. The pale yellow solid that is formed is isolated by filtration, yielding 1.86 g of 4- (4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1 H) - chloride - on-1-yl] -3-fluoro-phenylsulfonyl NMR spectra agree with the proposed structure This reaction is repeated to obtain additional product for the following reactions.

Step B: 4- (4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H] -on-1-yl) -3-fluorophenol. Hydrochloric acid gas is introduced into a mixture of 3.29 g (14.6 mmol) of tin chloride (II) in 40 ml of acetic acid, for about 5 minutes, turning into a clear solution, which is then heated to 85 ° C, and a hot solution of 1.66 g (4.85 mmol) of 4- (4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazole-5 (1 H) -on chloride -1-yl) -3-fluorophenylsulfonyl is added to the first solution, this reaction mixture is heated at 85 ° C for 45 min. After cooling to room temperature, the resulting yellow solution is poured into 120 ml of hydrochloric acid. To this mixture is added 100 ml of a saturated aqueous solution of sodium chloride, and the resulting mixture is extracted with ethyl acetate, but the layers do not separate. Addition of a saturated aqueous solution of sodium chloride makes a partial separation. aqueous it is extracted twice more with ethyl acetate, but all extracts are combined. After evaporation under reduced pressure, the residue retains a smell of hydrochloric acid. Water is added to the residue, and this mixture is extracted three times with ethyl acetate. The combined extracts are washed with water, dried over sulphate

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1250 anhydrous magnesium, and filter. After evaporation of the solvent under reduced pressure, the remaining yellow residue is dried in vacuo. The dry residue is placed on a silica gel column and eluted with methylene chloride / ethyl acetate (2: 1). After being dried in vacuo for several hours, 0.81 g of 4- (4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazole-5 (1 H) -on- is obtained. 1-yl) -3-fluortiophenol as a yellow syrup. The NMR spectra agree with the proposed structure. This reaction is repeated to obtain additional products for the following reactions.

Step C: 2- [2 - [- 4- (4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5- (1H) -on-1-yl] -3-fluorophenylthiomethyl] Methyl -5-chlorophenoxy] propionate By the method of Example 1, step I; 1.35 g (4.9 mmol) of 4- (4-difluoromethyl-4,5-dihydro-3-methyl-1,2, Methyl 2-(2-chloromethyl-5-chlorophenoxy) -propionate 4-triazole-5 (1H] -on-1yl) -3-fluorophenol and 3.0 g (11 mmol) (Example 2, step E) reacts in the presence of 1.02 g (7.4 mmol) of anhydrous potassium carbonate in 75 ml of Ν, Ν-dimethylformamide, resulting in 0.54 g of 2- (2- (4 (4-difluoromethyl-4,5) methyl-dihydro-3-methyl-1,2,4-triazol-5 (1H) -on-1-yl) -3-fluorophenylthiomethyl] -5-chlorophenoxy-] propionate in the form of a yellow syrup NMR spectra agree with the proposed structure NMR: 1.65 (d, 3H, J _HH = 8.0 Hz); 2.44 (3, 3H); 3.78 (s, 3H); 4.20 (dd, 2H, J _HH = 13 , or Hz); 4.78 (q, 1H, J _HH = 8.0 Hz); 6.70-7.38 (m, 7H).

Example 8. 2- (2- (4- (4-diflormethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H) -on-1-yl] 3-fluorophenoxymethyl] -5-methylphenoxy] methyl acetate (Compound 75)

Step A: Methyl (2-formyl-5-methylphenoxy] methyl acetate. By the method of Example 1, step F; 8.27 g (60 mmol) of 4-methylsalicylic aldehyde and 11.15 g (73 mmol) of bromacetate. of methyl reacts in the presence of 10.1 g (73 mmol) of anhydrous potassium carbonate in 150 ml of acetone, giving 11.47 g of methyl (2-formyl-5-methylphenoxy) methyl acetate as a white solid with a melting point 63 -64 ° C. The NMR agrees with the proposed structure.

Step B: Methyl (2-hydroxymethyl-5-methylphenoxy) methyl acetate. By the method of Example 1, step G 11.27 g (54 mmol) of methyl (2-formyl-5-methylphenoxy) -methyl acetate reacts with 0, 54 g (14 mmol) of sodium borohydride and 0.10 g (1.8 mmol) of sodium methoxide in 30 ml of methanol, yielding 9.41 g of methyl (2-hydroxymethyl-5-methylphenoxy) methyl acetate as a yellow oil The NMR spectrum is in agreement with the proposed structure.

Step C: Methyl (2-chloromethyl-5-methylphenoxy] methyl acetate. By the method of Example 1, step 9.21 g (44 mmol) of (2-hydroxymethyl-5-methylphenoxy) methyl acetate reacts with 7.40. g (62 mmol) of thionyl chloride and 5 drops of pyridine in 50 ml of methylene chloride, yielding 5.57 g of ethyl acetate (2-chloromethyl-5-methylphenoxy) as an orange liquid.

Step D: (2- [4- (4-diflormethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H) -on-1-yl) -3-fluorophenoxymethyl] -5-methylphenoxy / methyl acetate By the method of Example 1, step I 2.0 g (7.7 mmol) 1- (2-fluoro-4-hydroxyphenyl) -4-diflormethyl-4,5-dihydro-3-methyl-1 2,4-triazole-5 (1H) -one, example 1, step E and 3.53 g (15.1 mmol) of methyl acetate (2-chloroethyl-5-methylenoxy) react in the presence of 1.60 g (11, 6 mmol) of anhydrous potassium carbonate in 40 ml of Ν, Ν-dimethylformamide, yielding 2.75 g of

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RO 114254 Bl [2- [4- (4-diflormethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H) -on-1-yl) -3-fluorophenoxymethyl] - 5methylphenoxy] methyl acetate. The NMR spectrum confirms the proposed structure. NMR: 2.30 (s, 3H); 2.44 (s, 3H); 3.78 (s, 3H); 4.70 (s, 2H); 5.18 (s, 2H); 6.60-7.36 (m, 7H).

Example 9. 2-f3-f4-f4-d // 7ormet / M, 5-c // 77 / dro-3-met // - 7,2,4-tr / âzo / -5 / · 1H) - on-1-yl} -3-fluorophenoxymethyl] phenoxy] propionate. (Compound 80)

Step A: Methyl 2- [3-formylphenoxy) propionate. By the method of Example 1, step F 10.0 g (81.9 mmol) of 3-hydroxybenzene-aldehyde and 16.0 g (98.2 mmol) of methyl 2-bromopropionate react in the presence of 13.6 g (98.3 mmol) of anhydrous potassium carbonate in 50 ml of Ν, Ν-dimethylformamide, yielding 16.1 g of methyl 2- (3formylphenoxypipropionate as an orange liquid. NMR and IR spectra agree with the proposed structure.

Step B: Methyl 2- [3-formylphenoxy) propionate. By the method of Example 1, step G 15.7 g (76.1 mmol) of methyl 2- (3-formylphenoxy) propionate, 0.76 g (20 mmol) of sodium goride and 0.10 g (1.8 mmol) of sodium methoxide reacts in 40 ml of methanol, resulting in 15.6 methyl 2- (3-formylphenoxy) propionate as a yellow liquid. The NMR and IR spectra agree with the proposed structure.

Step C: Methyl 2- [3-chloromethylphenoxy) propionate. By the method of Example 1, step H 1.98 g (9.5 mmol) of 2- (3-hydroxymethylphenoxy) methyl propionate and 1.24 g (10.5 mmol) of thionyl chloride are reacted in the presence of five drops of pyridine in 40 ml of methylene chloride, yielding 1.93 g of methyl 2- (3-chloromethylphenoxypipropionate methyl as a yellow liquid. The NMR and IR spectra agree with the proposed structure.

Step D: 2- [3 - [- 4- [4-difluoromethyl-4,5-dihydro-3-1,2,4-triazol-5 [1H] -on-1-HJ-3-fluorophenoxymethyl] -phenoxy] methyl propionate.

By the method of Example 1, step I 1.0 g (3.8 mmol) of 1- (2-fluoro-4-hydroxymethyl-4,5-dihydro-3-methyl-1,2,4-triazole-5 (1H) -one, example 1, step F, and 1.72 g (7.6 mmol) of methyl 2- (3-chloromethylphenoxy] propionate react in the presence of 0.79 g (5.7 mmol) of anhydrous potassium carbonate. In 25 ml of N, N-dimethylformamide, yielding 1.54 g of 2- [3- [4- (4-diflormethyl-4,5-dihydro-3-methyl-1,2,4-triazole-5 (1H) -on- 1-yl) -3-fluorophenoxymethyl] phenoxy] methyl propionate NMR and IR spectra match the proposed structure NMR: 1.60 (d, 3H, J _HH = 8.0 Hz); 2.44 (s, 3H ); 3.76 (s, 3H); 4.78 (q, 1H, J _HH = 8.0 Hz); 5.04 (s, 2H); 6.76-7.38 (m, 8H)

Example 10. 2- [2- [4- (4-diflormethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 [1 H) -on-1-yl) -3-fluorophenoxymethyl] - phenoxy] methyl propionate. [Compound 81)

Step A: Methyl 2- (4-formylphenoxy) propionate. By the method of Example 1, step F 10.0 g (81.9 mmol) of 4-hydroxybenzaldehyde and 16.4 g (98.3 mmol) of 2- Methyl brompropionate reacts in the presence of 13.6 g (98.3 mmol) of anhydrous potassium carbonate in Ν, Ν-dimethylformamide, resulting in 12.2 g of methyl 2- (4-formylphenoxypipropionate as a yellow liquid. NMR spectra and IR agrees with the proposed structure.

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Step B: Methyl 2- [4-hydroxymethylphenoxy) propionate. By the method in the example

1, step G 11.1 g (53.3 mmol) of 2- (4-formylphenoxy) methyl propionate and 2.02 g 1330 (53.3 mmol) of sodium boride hydride reacts in methanol to yield 9.31 g 2 - (4-hydroxymethylphenoxy) methyl propionate as a yellow oil. The NMR spectrum agrees with the proposed structure.

Step C: Methyl 2- (4-chloromethylphenoxypipropionate) A mixture of 2.19 g (10.4 mmol) of 2- (4-hydroxymethylphenoxy) methyl propionate and 3.0 g (82.3 mmol) of 1335 acid. hydrochloric 36%, stirred for 15 minutes at room temperature, then the reaction mixture was poured into ice water, and the reaction mixture was extracted with diethyl ether. The extracts were combined and washed successively with water and a saturated aqueous solution. The extract is dried over anhydrous magnesium sulfate and filtered, and the solvent is evaporated from the filtrate under reduced pressure, leaving a colorless liquid 1340. This liquid is placed on a silica gel column and eluted with methylene chloride. After the product-containing fractions are combined and the solvent is evaporated under reduced pressure, 1.6 g of methyl 2- (4-chloromethylphenoxy) -propionate are isolated in the form of a colorless liquid, the NMR and IR spectra agree with the proposed structure.

Step D: 2- [4- [4- [4-diflormethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5 (1H) -on-1-HJ-3-fluorophenoxymethyl] -phenoxy ] -methyl propionate. By the method of Example 1, step 1, 0.50 g (1.9 mmol) of 1- (2-fluoro-4-hydroxyphenyl] -4-diflormethyl-4,5-dihydro-3-methyl-1,2, Methyl 4-triazole5 (1H) -one (example 1, step E) and 0.87 g (3.8 mmol) of 2- (4-chloromethylphenoxy) propionate react in the presence of 0.2 g of 1.4, 7,10,13,16- 1350 hexaoxacycloactadican in 15 ml of Ν, Ν-dimethylformamide, yielding 0.80 g of 2- / 4 / 4- (4-diflormethyl-4,5-dihydro-3-methyl-1, 2,4-Triazol-5 (1H) -on-1-yl) -3-fluorophenoxymethyl / phenoxy / methyl propionate substances form a colorless solid that solidifies when standing, mp 83-85 ° C. NMR spectra and IR match the proposed structure: MRI: 1.60 (d, 3H, J = 8.0 Hz); 2.44 (s, 3H); 3.76 (s, 3H); 4.78 1355 (q, 1H, J = 8.0 Hz); 4.90 (s, 2H); 6.78-7.38 (m, 8H).

Example 11. 2- [2- [4- (8-thia-1,6-diazabicyclo [4.3, O] nonan-7-on-9-ylimino) -3-fluorophenoxy-methyl] -5-methylphenoxy] prpionate [ Compound 68)

Step A: Methyl 2- [2- [3-fluoro-4-nitrophenoxymethyl] -5-methylphenoxy] propionate. By the method of Example 1, step I, 1.71 g (10 mmol) of 3-fluoro-4-nitro-phenol and 2.85 1360 g (11 mmol) of 2- (2-chloromethyl-5-methylphenoxy) propionate of methyl reacts in the presence of 1.66 g (12 mmol) of anhydrous potassium carbonate in 100 ml of Ν, Ν-dimethylformamide, resulting in 3.55 g of 2- / 2- (3-fluoro-4-nitrophenoxymethyl) - Methyl 5-methylphenoxy / -propionate substances form a yellowish solid, mp 92-94 ° C. The NMR and IR spectra agree with the proposed structure. 1365

Step B: Meth 2- [2- [4-amino-3-fluorophenoxymethyl) -5-methylphenoxy] -propionate. By the method of Example 2, methyl step 3.35 g (9.1 mmol) of methyl 2- [2- (3-fluoro-4-nitrophenoxymethyl] -5-methylphenoxy] -propionate reacts with 2.8 g ( 50 mmol) of iron powder in 100 ml of acetic acid, yielding 1.86 g of methyl substances 2- [2- (4-amino-3-fluorophenoxymethyl) -5RO 114254 Bl-methylphenoxy] -propionate as a brown syrup. The NMR and IR spectra agree with the proposed structure.

Step C: Methyl 2- [2- [3-fluoro-4-isothiocyanatephenoxymethyl} -5-methylphenoxy] -propionate. A solution of 1.66 g (5 mmol) of 2- [2- (4-amino-3-fluorophenoxymethyl) -5-methylphenoxy] methyl propionate and 1.26 g (12.5 mmol] of triethylamine in 40 ml of methylene chloride is prepared at room temperature To this solution is added dropwise a solution of 0.58 g (5 mmol) of thiophosene in 10 ml of methylene chloride. The reaction mixture is stirred for 16 hours and then stirred. filter through a short column of silica gel. The solvent is evaporated from the filtrate under reduced pressure, leaving 1.50 g of methyl 2- (2- (3-fluoro-4-isothiocyanatophenoxymethyl) -5-methylphenoxy] -propionate as a The NMR and IR spectra agree with the proposed structure.

Step D: Methyl 2- [2- [4- (perhydropyridazyl-1-yl-thiocarbonylamino] -3-fluorophenoxy-methyl)] 5-methylphenoxy-propionate. By the method of Example 1, step C, of U.S. Patent 4,906,281.1,50 g (4 mmol) of 2- / 2- (3-fluoro-4-isothiocyanatephenoxymethyl) -5-methylphenoxy / methyl propionate and 1, 07 g (5 mmol) of perhydropyridazine monohydrate, prepared by the method of Example 1, step B, of US Patent 4,906,281, reacts in the presence of 0.20 g (5 mmol) of sodium hydroxide in 40 ml of water and 10 ml of tetrahydrofuran, yielding 1.50 g of methyl 2- / 2- / 4- (perhydropyridazine-1-ylcarocarbonylamino) -3-fluorophenoxy-methyl) -5-methylphenoxy / -propionate substances. The NMR spectrum confirms the proposed structure.

Step E: 2- [2- [4- [8-thia-1, B-diazabicyclo- [4,3, O] nonan-7-on-yl-imino] -3-fluorophenoxymethyl] -5-methylphenoxy] - methyl propionate. By the method of Example 1, step D of US Patent 4,906,281, 1.50 g (3.25 mmol) of 2- (2- (4- (perhydropyrazin-1-ylcarocarbonylamino) -3-fluorophenoxymethyl] -5-methylphenoxy) ] -methyl propionate and 0.36 g (90.17 mmol) of chloromethyl chlorformate react in the presence of 0.36 g (3.5 mmol) of triethylamine in 35 ml of dioxane, yielding 0.50 g of 2- Methyl (2- (4- (8-thio-1,6-diazabicyclo [4,3, O] nonan-7-on-9 -) - 3-fluorophenoxymethyl) -5-methylphenoxy] -propionate syrup substances NMR and IR spectra agree with the proposed structure NMR: 1.60 (d, 3H, J = 8.0 Hz); 1.78-1.96 (m, 4H); 2.30 (s, 3H); 3.64-3.80 (m, 4H); 3.70 (s, 3H); 4.80 (q, 1H, j = 8.0 Hz); 5.10 (dd, 2H); 6.58 -7.30 (m, 6H).

Example 12. Methyl 2- [2- [4-1-methyl-7-trifluoromethyl-2,4- (1H, 3H] -pyrimidindion-3-yl) phenoxymethyl] -5-methylphenoxy] -propionate. [Compound 87]

Step A: 1-Methyl-3- [4-methoxyphenyl] -6-tinfluoromethyl-2,4- [1H, 3H] -pyrimidine-dione. 8.27 g (207 mmol) of a suspension of 60% sodium hydride in mineral oil is placed in a vessel. The mineral oil is removed by washing sodium hydride twice with heptane. Then 300 ml of tetrahydrofuran is added to the vessel. This suspension is cooled to -20 ° C which is maintained during the dropwise addition of 37.9 g (207 mmol) of 3-amino-4,4,4-trifluorcrotonoate. This mixture is allowed to stir for 10 minutes before the dropwise addition of 30.83 g (207 mmol) of 4-methoxyphenyl isocyanate begins. After completion of the addition, the reaction mixture is heated to reflux for about 16 h. At the end of this period the reaction mixture is cooled to room temperature, and 28.56 (207

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1415 mmol) of potassium carbonate and 58.75 g (228 mmol) of methyl iodide were added. The reaction mixture is heated to reflux for seven hours. At the end of this period the reaction mixture is cooled, and diethyl ether and water are added. The aqueous phase is separated from the organic phase. The latter is washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate is concentrated under reduced pressure, leaving a residue. The residue is passed through a column of silica gel, eluting with ethyl acetate / heptane mixtures, starting with 1: 8 and ending with 1: 1. The fractions containing the product are combined, and the solvent is evaporated under reduced pressure, resulting

27.1 g of 1-methyl-3- (4-methoxyphenyl) -6-trifluoromethyl-2 _L 4- (1H, 3H) -pyrimidinedione. The NMR spectrum confirms the proposed structure.

Step B: 7-Met / 7-3-4-h / c / roxifen / 77-6-tr / Q / trifluoromethylsulphinyl // - _2/4 - / '7 H, 3 H] -pyrimidinedione. 25.88 g (86 mmol) of 1-methyl-3- (4-methoxyphenyl) -6-trifluoromethyl- is placed in a vessel.

2,4- (1H, 3H) -pyrimidindione and 200 ml of methylene chloride. 258 ml (258 mmol) of solution, 1 mol of boron tribromide in methylene chloride are added dropwise to this vessel. Upon completion of the addition, the reaction mixture is stirred at room temperature for about 64 h and then poured into ice. This mixture is filtered to remove the insoluble material and the aqueous and organic layer of the filtrate is separated. The organic slurry was washed with water, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure, leaving 1-meth 1-3- (4-hydroxyphenyl) -6-trifluoromethyl-2,4- (1H, 3H) -pyrimidindione as a residue. The NMR spectrum confirms the proposed structure.

Step C: Methyl 2- [2- [4- (1-methyl-6-trifluoromethyl-2,4- (1H, 3H] -pyrimidindion-3-yl] -phenoxymethyl] -5-methylphenoxy] propionate. of example 1, step 1, 0.7 g (2.9 mmol) of methyl 2- (2-chloromethyl-5-methylphenoxy) propionate, example 1, step H, 0.30 g (1.1 mmol) of 1 -methyl-3- (4-hydroxyphenyl) -6-trifluoromethyl-2,4- (1H, 3H) -pyrimidindione, and 0.22 g (1.6 mmol) of potassium carbonate reacts in 80 ml of Ν, Dimethylformamide, yielding 0.33 g of 2- / 2- / 4- (1-methyl-6-trifluoromethyl-2,4- (1H, 3H-pyrimidindion-3-yl) -phenoxymethyl / -5-methylphenoxy / methyl propionate (Compound 87) substances form a yellow solid with mp 52-54 ° C. The NMR and IR spectra agree with the proposed structure.

The compounds according to the invention, 2 - [(4-heterocyclicsubstituted-3-halophenoxymethyljphenoxy) alkanoates are unexpectedly active as both post- and pre-emergent herbicides, in particular, as preparation herbicides many of these compounds have the tolerance of soy and beans. To a certain extent, corn is of greater interest to the post-emergence activity, where harvest tolerance is required, making them excellent candidates for total vegetation control.

The following shows the herbicidal activity of the compounds according to the invention.

The 2 - [(4-heterocyclicsubstituted-3-halophenoxymethyl) phenoxy / alkanoate derivatives of this invention are tested in pre- and post-emergence assessments using a variety of large leaf and herbs or weeds. Species for testing usually demonstrate that the herbicidal activity of these compounds includes soy [Glycine max, var. Wiliams], field corn (Zea mays var. Agway 425 λ), wheat [Triticum aestivum var.

Wheaton], zhle [Ipomea lacunosa or Ipomea hederaceâ], holus [Abutilon theophrasti),

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RO 114254 Blade of the green foxtail (Setaria viridis), Johnson grass [Sorghum halepease], foxtail [Alapecurus myosurcides), common rockfish [Stellaris media], ordinary poppy seedlings [Xanthium pensylvanicum].

Preparation of fiber vessels.

For the pre-emergence test two available fiber vessels (8 cm x 15 cm x 25 cm) for each apical quantity of each herbicidal candidate are filled to a depth of approximately 6.5 cm of steam sterilized clay sandy soil. The ground is level 3i printed with a pattern to ensure five furrows spaced 13 cm long and 0.5 cm deep on each blade. Soybeans, wheat, corn, green fox tail and Johnson grass are planted in the furrows of the first vessel and seeds of holcus, zhle, common mackerel, poppy seeds and foxtail are planted in the furrows of the second vessel. The five-row pattern is used to push the seeds firmly into place. The top soil with equal portions of sand and clayey sandy soil is planted evenly above each vessel at a depth of about 0.5 cm. The pots for post-emergence testing are prepared in the same way, except that they are planted 8-12 days before the pre-dawn ones and planted in a greenhouse and watered, thus allowing the seeds to germinate and the leaves to germinate. develop.

A solution stored from the herbicidal candidate is prepared by dissolving a predetermined amount of the compound in 20 ml of water / acetone (50:50) containing 0.5% v / v sorbitan monolaurate. Thus, for the application of 3000 g / ha of herbicide, 0.21 g of herbicidal candidate is dissolved in 20 ml of aqueous acetone to prepare the stock solution. For the amount of 300 g / ha of application used in most of the tests reported below, a portion of the stored solution of 1.0 ml is diluted with water / acetone (50:50) to 35 ml, the volume required for a spray volume of 1000 l / ha. The remaining stock solution is then used to prepare spray solutions for other application quantities.

The spray solution, 35 ml, is then sprayed on four vessels simultaneously, that is, on the soil surface in the pre-dawn vessels and on the foliage that appeared in the post-dawn vessels. All vessels are placed in the greenhouse, but only the pre-dawn vessels are immediately watered. The leaves in the post-dawn pots are kept dry for 24 hours, after which regular watering begins. Phytotoxicity data, taken as a percentage of control, are recorded 17-21 days after the chemicals are applied.

Percent control was determined by a similar method by a count of 100 A to the system described in Weed Research meth Science ^", 2nd ed., B. Truelove, Ed .; Southern weed Science Society; Auburn University, Auburn, Alabama, 1977, The dosage system is as follows.

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The herbicidal quantitative system

Quantity percentage control Description of the main effect Harvest description Description of weeds 0 No effect No reduction or damage to the crop No weed control 10 Easy Light discoloration or discoloration Very poor weed control 20 effect Light discoloration, discoloration or loss Poor weed control 30 Harvest of crop more pronounced but not lasting Weak to deficient weed control 40 Effect Moderate affect is usually the crop Poor weed control 50 moderate More sustainable affectation of the crop doubtful return. Poor to moderate weed control 60 Strongly affected crop, he does not recover Moderate weed control 70 Severe Strong affectation and bearable loss Control less than satisfactory 80 Almost destroyed, a few survivors Weed control satisfactory to good 90 Only a few plants remained Good to excellent 100 Full effect Complete destruction of the crop Complete destruction of weeds

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Herbicidal data of 300 or 250 g / ha are presented in Table 2 (pre-emergence activity) and Table 4 (post-emergence activity). The test compounds are identified in Tables 2 and 3 by numbers that correspond to those in Table 1.

For herbicide application the active compounds are formulated in herbicidal compositions by mixing in herbicide effective amounts with adjuvants and carriers normally used in the environment to facilitate dispersion of the active ingredients for the particular intended use, recognizing that the formulation and application of a toxic may affect the activity of the material in a given application. Thus, for agricultural use the present herbicidal compounds can be formulated as granules with a size of

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RO 114254 The relatively large particle, as water-soluble or dispersible granules, as powders, as wettable powders, as emulsifiable concentrates, as solutions or as any of several known types of formulations, depending on the desired mode of application.

These herbicidal compositions can be applied either as water diluted sprays, or powders or granules in areas where vegetation suppression is desired. These formulations may contain from 0.1%, 0.2% or 0.5% to even 95% or more by weight of the active ingredient.

The powders are blends that flow alone, of active ingredient, with finely divided solids, such as talc, natural clays, diatomite, flours such as walnut and cottonseed, and other organic and inorganic solids that act as dispersants or carriers for poison; these finely divided solids have an average particle size of less than about 50 microns. A typical powder formulation useful here is one containing one part or less of herbicidal compound and 99 parts of talc.

Wettable powders, formulations, also useful for both pre- and post-emergence herbicides, are in the form of finely divided particles that disperse very easily in water or any other dispersant. The wettable powder is finally applied to the soil in the form of a dry powder or as an emulsion in water or other liquid. Typical carriers for wettable powders include Fuller's soil, kaolinic clays, silica and other strong absorbers, inorganic diluents readily moisturized. The wettable powders are usually prepared to contain about 5-80% of the active ingredient, depending on the absorbency of the carrier, and typically also contain a small amount of a wetting, dispersing or emulsifying agent to facilitate dispersion. For example, a useful wettable powder contains 80.8 parts of herbicidal compound, 17.9 parts of clay. Palmetto and one part of sodium lignosulphonate and 0.3 parts of aliphatic polyester sulphonated as wetting agents. Frequently additional wetting agent and / or oil is added to the mix in the vessel for post-emergence application to mow the foliage dispersion and absorption by the plant.

Other formulations useful for herbicidal applications are emulsifiable concentrates (ECs) which are homogeneous liquid compositions dispersible in water or another dispersant, and may consist entirely of the herbicidal compound and a liquid or solid emulsifying agent, or may also contain a carrier. liquid, such as xylene, strong aromatic naphthalene, isophorone or other non-volatile organic solvent. For herbicidal application these concentrates are dispersed in water or another liquid carrier, and are normally sprayed on the area to be treated. The weight percentage of the main active ingredient may vary depending on how the composition is applied, but generally comprises 0.5 to 95% by weight of the herbicidal composition.

The flowing formulations are similar to the EC except that the active ingredient is suspended in a liquid carrier, generally water. Flowing formulations, such as CEs, may include a small amount of surface active agent, and contain active ingredient from 0.5 to 95%, often from 10 to 50% by weight of the composition. For application, the flowing formulations can be diluted in water or other liquid vehicle, and are normally spray-applied to the area to be treated.

Typical wetting, dispersing or emulsifying agents used in agricultural formulations include, but are not limited to, alkyl and alkyl sulfonates and their salts.

RO 114254 Sodium bl; alkylaryl polyester alcohols; sulphonates of higher alcohols; polyethylene oxides; sulphonated animal and vegetable oils; sulphonated petroleum oils; 1565 fatty acid esters of polyhydric alcohols and ethylene oxide addition products of these types of esters; and the addition product of long-chain mercaptan and ethylene oxide. Many other types of surface active agents users are in the trade. Surface active agent, when used, typically comprises from 1 to 15% by weight of the composition. 1570

Other useful formulations include suspensions of the active ingredient in a relatively non-volatile liquid such as water, corn oil, kerosene, propylene glycol, or another suitable liquid carrier.

Other liquid formulations for herbicidal applications include simple solutions of the active ingredient in a solvent which can be completely dissolved in the desired concentration 1575, such as acetone, alkylated naphthalenes, xylene or other organic solvents. Granular formulations, where the toxic substance is in the form of relatively small particles, are of particular utility for air distribution or for penetrating crop cover. Pressurized sprays, typically aerosols where the active ingredient is dispersed into a finely divided form as a result of vaporizing a low boiling dispersible 1580 solvent carrier, such as Freon fluorinated hydrocarbons, may also be used. Water soluble or dispersible granules are also useful formulations for the herbicidal application of the present compounds. Such granulated formulations flow freely, are not in powder form and are easily soluble or miscible in water. Soluble or dispersible granular formulations described in US Patent No. 1585 3,929,442 are useful with the herbicidal compounds present. Used by the farmer on the field, granular formulations, concentrated emulsifiable flowing concentrations, solutions, etc., can be diluted with water to give a concentration of the active ingredient from 0.1% or 0.2% to 1.5% or 2%. The active herbicidal compounds of this invention can be formulated and / or applied with insecticides, fungicides, 1590 nematocides, plant growth regulators, fertilizers or other agricultural chemicals and can be used as efficient soil sterilizers and selective herbicides in agriculture. By applying an active compound of this invention, formulated alone or with other agricultural chemicals, of course, an efficient amount and concentration of the active compound is used; the amount may be for example about 10 to 1595 100 g / ha, preferably 30 to 60 g / ha. For field use, where there are herbicide losses, larger amounts of application can be used, for example four times the quantities of greenhouse test mentioned above.

The active herbicidal compounds of this invention may be used in combination with other herbicides, for example, they may be mixed with, say, a smaller, equal, or greater than 1600 amount of a known herbicide such as chloracetanilide, herbicides such as 2-chloro- N (2,6-diethylphenyl] -N- (methoxymethyl) acetylamide (alachlor), 2-chloro-N- (2-ethyl-6-methylphenyl] -N- (2-methoxy-1-methylethyl) -acetamide (metalachlor), and N-chloroacetyl-N- (2,6-diethylphenyl] glycine (diethyl ethyl]; benzothiadiazonine herbicides such as 3- (1-methylethyl] - (1H-2,1,3-benzethiadiazin-4- (3H ) -one-2,2-dioxide (bentazone); herbicides, traysinics such as 6-chloro-N-ethyl-N- (1- 1605 methylethyl) -1,3,5-triazine-2,4-diamine ( atrazine), and 2- / 4-chloro-6- (ethylamine) -1,3,5-triazin-2yl / amino-2-methylpropannitrile (cyanazine); dimitroaniline herbicides such as 2,6-dinitroN, N- dipropyl-4- (trifluoromethyl] -benzenamine [trifluralia]; urea herbicides such as N '(3,4-dichlorophenyl] -N, N-di-methylureas (diurene) and N, N-dimethyl-N'- /3- (Trifluoromethyl] phenyl / urea

RO 114254 Bl (fluoromethane); and 2 - / (2-chlorophenyl) methyl / -4,4-dimethyl-3-isoxazolidione.

It is possible that different modifications may be made in the formulation and application of the compounds of this invention without departing from the concepts of the present invention as is apparent from the claims.

Table 3

Herbicide activity before sunrise [% control]

Compound no. Quantity (kg / ha) 103 2 0.3 3 0.25 4 0.3 Species soy □ 0 90 80 Wheat 7C 80 20 80 Corn 15 15 15 70 Holcus 1OG 100 100 100 Morning Glory 100 100 100 100 Rocinante 90 80 90 100 Thistle-priest 10 20 70 80 Tail fox 80 40 70 80 Tail fox green 90 80 100 100 Johnson's leg 80 70 70 95 Compound no. 5 6 7 8 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 10 10 50 0 Wheat 10 50 95 0 Corn 20 85 10 5 Holcus 100 100 100 85 Morning Glory 100 100 100 85 Rocinante 100 100 100 90 Thistle-priest 70 100 100 0 Tail fox 90 100 100 0 Tail fox green 100 100 100 10 Johnson's leg 95 80 70 40

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Compound no. 9 10 11 12 Quantity (kg / ha) □ .3 0.3 0.3 0.3 Species soy 100 10 0 20 Wheat 80 20 10 70 Corn 95 10 10 50 Holcus 100 100 100 100 Morning Glory 100 95 100 100 Rocinante 100 100 100 100 Thistle-priest 100 10 60 90 Tail fox 100 70 20 80 Tail fox green 100 100 100 100 Johnson's leg 95 40 90 60 Compound no. 13 14 15 16 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 0 0 0 10 Wheat 0 5 5 15 Corn 5 10 5 15 Holcus 100 85 100 100 Morning Glory 60 70 100 100 Rocinante 20 45 90 100 Thistle-priest 30 0 5 60 Tail fox 0 0 0 20 Tail fox green 85 75 50 100 Johnson's leg 10 30 0 60 Compound no. 17 18 19 20 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 10 0 60 0 Wheat 70 10 0 Corn 10 30 20 0 Holcus 100 100 100 100 Morning Glory 30 90 90 80

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Compound no. 17 18 19 20 Rocinante 40 100 100 50 Thistle-priest 20 40 60 □ Tail fox 80 10 90 10 Tail fox green 90 100 100 100 Johnson's leg 90 90 90 60 Compound no. 21 22 2. 3 24 Quantity (kg / ha) 0.3 0.3 0.3 0.25 Species soy 0 10 - 5 Wheat □ 60 5 10 Corn 30 50 5 5 Holcus 100 100 30 80 Morning Glory 70 90 100 70 Rocinante 20 80 85 95 Thistle-priest 20 10 0 20 Tail fox 10 30 5 90 Tail fox green 95 95 40 30 Johnson's leg 70 50 60 15

* The average of two tests - in which the average is not a multiple of five, given that the next multiple is less than five

Compound no. 25 26 27 28 Quantity (kg / ha) □ 3 0.3 0.3 0.3 Species soy 20 0 10 90 Wheat 20 □ 0 95 Corn 10 0 15 95 Holcus 100 85 100 50 Morning Glory 100 95 100 20 Rocinante 100 100 85 Thistle-priest 80 10 80 0 Tail fox 0 40 70 60 Tail fox green 60 20 0 15 Johnson's leg 10 0 40 85

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Compound no. 29 30 31 32 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 30 40 10 30 Wheat □ 0 0 0 Corn 20 □ □ 0 Holcus 100 85 100 100 Morning Glory 100 90 95 100 Rocinante 100 95 10 100 Thistle-priest 85 100 20 80 Tail fox - 30 10 30 Tail fox green 95 70 0 100 Johnson's leg 80 10 10 10 Compound no. 33 34 35 36 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 0 0 0 0 Wheat 0 0 0 0 Corn 15 0 10 0 Holcus 100 95 100 100 Morning Glory 100 90 95 80 Rocinante 100 - 95 100 Thistle-priest 10 10 10 20 Tail fox 0 10 10 10 Tail fox green 70 0 0 10 Johnson's leg 10 0 20 0 Compound no. 37 34 39 40 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 0 0 10 10 Wheat 0 0 10 Corn □ 0 - 0 Holcus 80 70 0 0 Morning Glory 60 20 10 a

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Compound no. 37 34 39 40 Rocinante 0 50 100 Thistle-priest 0 10 0 10 Tail fox □ 0 0 1750 Tail fox green 10 40 0 Johnson's leg 10 10 20 10 Compound no. 41 42 43 44 Quantity (kg / ha) 0.3 0.3 0.3 0.3 1755 Species soy 0 0 0 20 Wheat 0 0 0 0 Corn 20 50 30 20 Holcus 0 0 80 Morning Glory 10 0 0 80 1760 Rocinante 0 0 0 80 Thistle-priest 10 20 0 70 Tail fox 0 0 0 10 Tail fox green 10 0 0 20 Johnson's leg 30 0 20 30 1765 Compound no. 45 46 47 48 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 0 20 30 90 Wheat 0 10 75 90 1770 Corn 0 10 75 95 Holcus 0 100 100 100 Morning Glory - 95 100 100 Rocinante 0 100 100 100 Thistle-priest • 60 75 100 1775 Tail fox 0 40 95 95 Tail fox green 0 100 100 100 Johnson's leg 0 90 75 75

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Compound no. 49 50 51 52 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 75 60 80 90 Wheat 85 75 80 20 Corn 75 30 75 60 Holcus 100 100 100 100 Morning Glory 100 85 100 100 Rocinante 100 100 100 100 Thistle-priest 100 75 85 95 Tail fox 90 80 80 40 Tail fox green 100 80 95 90 Johnson's leg 100 80 95 90 Compound no. 53 54 55 56 Quantity (kg / ha) 0.3 • 0.3 0.3 □ 3 Species soy 100 95 70 90 Wheat 80 0 20 50 Corn 40 30 30 40 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 90 50 80 75 Tail fox 100 20 75 75 Tail fox green 100 95 95 100 Johnson's leg 70 70 75 95 Compound no. 57 58 59 60 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 40 60 50 75 Wheat 80 75 20 20 Corn 75 40 20 20 Holcus 100 100 100 100 Morning Glory 100 100 85 100

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Compound no. 57 58 59 60 Rocinante 100 100 90 100 Thistle-priest 70 30 75 60 Tail fox 80 75 70 60 Tail fox green 100 100 90 100 Johnson's leg 80 90 80 70 Compound no. 61 62 63 64 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 40 40 40 30 Wheat 20 70 10 20 Corn 20 50 10 30 Holcus 100 100 100 100 Morning Glory 80 100 100 100 Rocinante 70 100 100 100 Thistle-priest 10 60 75 60 Tail fox 40 85 70 30 Tail fox green 40 85 70 30 Johnson's leg 70 80 75 30 Compound no. 65 66 67 68 Quantity (kg / ha) 0.3 0.3 □ 3 0.3 Species soy 85 10 10 40 Wheat 10 10 10 10 Corn 10 0 10 10 Holcus 100 80 100 100 Morning Glory 80 10 100 90 Rocinante 100 0 60 100 Thistle-priest 80 10 30 40 Tail fox 50 30 60 30 Tail fox green 100 0 75 80 Johnson's leg 80 0 10 40

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Compound no. 69 70 71 72 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 60 20 85 40 Wheat 40 40 20 40 Corn 20 30 30 60 Holcus 100 100 100 100 Morning Glory 80 100 100 100 Rocinante 100 100 100 100 Thistle-priest 90 30 85 75 Tail fox 40 0 □ 75 Tail fox green 100 100 100 90 Johnson's leg 95 20 75 50 Compound no. 73 74 75 76 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 0 10 10 20 Wheat 0 80 60 60 Corn 0 20 20 70 Holcus 100 100 100 100 Morning Glory 80 100 100 100 Rocinante 100 80 75 80 Thistle-priest 20 □ 10 30 Tail fox 70 95 75 60 Tail fox green 100 80 100 100 Johnson's leg 30 70 70 80 Compound no. 77 78 79 80 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 10 10 □ 0 Wheat 5 20 10 85 Corn 10 10 20 5 Holcus 10 100 100 100 Morning Glory 80 100 95 100

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Compound no. 77 78 79 80 Rocinante 20 30 95 90 Thistle-priest 10 60 0 20 Tail fox 5 30 40 50 Tail fox green 20 80 70 100 Johnson's leg 20 50 95 80 Compound no. 81 82 83 84 Quantity (kg / ha) 0.25 0.25 0.25 0.25 Species soy 0 0 0 10 Wheat 0 5 5 0 Corn 10 40 5 5 Holcus 50 95 0 0 Morning Glory 80 85 0 10 Rocinante 15 30 90 5 Thistle-priest 20 40 0 5 Tail fox 60 60 0 0 Tail fox green 95 85 30 Johnson's leg 10 80 5 10 Compound no. 85 86 87 88 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 60 85 75 ⁹⁰ Wheat 10 30 50 0 Corn 75 75 60 20 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 45 100 70 50 Tail fox 90 75 60 20 Tail fox green 100 90 95 100 Johnson's leg 90 95 95 30

RO 114254 Bl

Compound no. 89 90 91 92 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 100 100 100 95 Wheat 30 90 10 0 Corn 75 90 90 60 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 100 95 90 95 Tail fox 95 60 85 40 Tail fox green 100 100 100 100 Johnson's leg 100 100 100 95 Compound no. 93 94 95 96 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 40 100 90 95 Wheat 20 0 10 60 Corn 40 45 85 60 Holcus 100 100 100 100 Morning Glory 100 100 95 100 Rocinante 100 100 100 100 Thistle-priest 75 100 100 90 Tail fox 75 85 70 40 Tail fox green 70 100 100 100 Johnson's leg 75 100 95 75 Compound no. 97 98 99 100 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 95 10 20 50 Wheat 20 0 0 0 Corn 30 20 20 60 Holcus 100 100 100 100 Morning Glory 100 60 20 90

RO 114254 Bl

Compound no. 97 98 99 100 Rocinante 1OO 100 ND 100 Thistle-priest 90 40 40 80 Tail fox 30 0 20 20 Tail fox green 95 70 100 100 Johnson's leg 60 40 80 80 Compound no. 101 102 103 104 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 70 75 60 100 Wheat 10 0 60 20 Corn 75 10 80 60 Holcus 100 100 100 100 Morning Glory 60 60 100 100 Rocinante 100 95 100 100 Thistle-priest 60 70 90 80 Tail fox 30 0 95 80 Tail fox green 95 100 100 100 Johnson's leg 60 100 95 95

Table 4

Herbicidal activity after sunrise [% Contr.]

Compound no. Quantity (kg / ha) 1 0.3 2 0.3 3 0.25 4 0.3 Species soy 60 85 95 95 Wheat 85 100 95 95 Corn 70 100 95 100 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 90 100 100 Thistle-priest 50 100 100 100 Tail fox 30 90 95 100 Tail fox green 100 100 100 100

RO 114254 Bl

1980

Compound no. Amount (Kg / ha) 1 □ .3 2 0.3 3 0.25 4 0.3 Johnson's leg 8C 100 90 100 Compound no. 5 6 7 8 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 80 90 95 40 Wheat 95 100 100 20 Corn 100 100 100 40 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 40 Thistle-priest 40 100 100 0 Tail fox 100 100 100 70 Tail fox green 95 100 90 10 Johnson's leg 95 80 70 40 Compound no. 9 10 11 12 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 100 95 80 95 Wheat 100 100 95 100 Corn 95 10 10 50 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 95 100 100 Thistle-priest 100 95 100 Tail fox 100 100 95 100 Tail fox green 100 100 100 100 Johnson's leg 100 95 100 100 Compound no. 13 14 15 16 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 70 50 50 75 Wheat 20 50 95 100

1985

1990

1995

2000

2005

010

RO 114254 Bl

Compound no. 13 14 15 16 Corn 75 75 95 95 Holcus 80 100 100 100 Morning Glory 60 100 100 100 Rocinante A 5 10 100 Thistle-priest 60 55 60 100 Tail fox 5 10 5 60 Tail fox green 20 90 100 100 Johnson's leg 40 35 70 95 Compound no. 17 18 19 20 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 60 85 60 70 Wheat 30 100 100 95 Corn 95 100 100 100 Holcus 100 100 100 100 Morning Glory 95 100 100 100 Rocinante 20 100 100 80 Thistle-priest 80 100 100 90 Tail fox 10 95 100 70 Tail fox green 30 100 100 100 Johnson's leg 85 100 95 100 Compound no. 21 22 2. 3 24 Quantity (kg / ha) 0.3 0.3 0.3 0.25 Species soy 30 70 40 90 Wheat 20 100 15 20 Corn 30 90 30 100 Holcus 95 100 80 100 Morning Glory 100 100 100 100 Rocinante 20 95 40 100 Thistle-priest 80 - 20 100 Tail fox 20 95 5 60

RO 114254 Bl

2045

Compound no. 21 22 2. 3 24 Tail fox green 95 1OO 15 85 Johnson's leg 90 70 10 70

* The average of two tests - in which the average is not a multiple of five, given that the next multiple is less than five

Compound no. 25 26 27 28 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 75 60 95 95 Wheat 10 20 15 90 Corn 75 75 100 80 Holcus 100 60 100 90 Morning Glory 100 100 100 95 Rocinante 100 20 100 95 Thistle-priest 100 100 100 70 Tail fox 0 0 10 85 Tail fox green 80 0 90 20 Johnson's leg 95 10 50 40 Compound no. 29 30 31 32 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 90 90 40 95 Wheat 30 20 15 10 Corn 80 80 100 80 Holcus 100 100 100 100 Morning Glory 100 95 100 100 Rocinante 100 95 30 100 Thistle-priest 90 100 85 - Tail fox 0 10 0 0 Tail fox green 50 80 80 60 Johnson's leg 0 60 30 20

2050

2055

2060

2065

2070

RO 114254 Bl

Compound no. 33 34 35 36 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 70 10 60 40 Wheat A 10 15 0 Corn 50 25 25 80 Holcus 100 50 100 100 Morning Glory 100 90 100 100 Rocinante 80 100 95 Thistle-priest 80 10 80 95 Tail fox 10 0 0 0 Tail fox green 20 0 50 30 Johnson's leg 0 0 50 0 Compound no. 37 34 39 40 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 30 20 10 0 Wheat 15 0 0 0 Corn 10 60 10 15 Holcus 85 80 10 0 Morning Glory 50 100 0 0 Rocinante 10 80 20 0 Thistle-priest 60 - 0 0 Tail fox 10 0 0 0 Tail fox green 10 30 20 0 Johnson's leg 4 0 0 0 Compound no. 41 42 43 44 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 30 70 30 80 Wheat 0 10 0 40 Corn 30 40 0 70 Holcus 100 85 70 100 Morning Glory 100 100 85 100

RO 114254 Bl

Compound no. 41 42 43 44 Rocinante - 70 0 90 Thistle-priest 90 60 100 Tail fox 0 0 0 0 Tail fox green 20 30 10 20 Johnson's leg 50 30 30 10 Compound no. 45 46 47 48 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 50 60 80 95 Wheat 0 90 95 100 Corn 40 75 100 100 Holcus 60 100 100 100 Morning Glory 80 100 100 100 Rocinante 0 100 100 100 Thistle-priest 95 100 100 100 Tail fox 0 80 100 100 Tail fox green 30 100 100 100 Johnson's leg 70 100 100 100 Compound no. 49 50 51 52 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 75 95 100 100 Wheat 95 90 95 100 Corn 50 90 100 100 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 100 100 100 100 Tail fox 100 100 100 85 Tail fox green 100 100 100 100 Johnson's leg 100 100 95 100

2140

RO 114254 Bl

Compound no. 53 54 55 56 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 100 100 90 90 Wheat 100 60 70 95 Corn 80 70 50 60 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 95 100 Thistle-priest 100 100 100 100 Tail fox 100 60 90 95 Tail fox green 100 100 100 100 Johnson's leg 100 100 95 100 Compound no. 57 58 59 60 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 80 95 90 100 Wheat 85 100 95 90 Corn 100 100 60 - Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 100 95 100 100 Tail fox 95 100 90 75 Tail fox green 100 100 100 100 Johnson's leg 100 100 100 100 Compound no. 61 62 63 64 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 95 85 85 75 Wheat 40 90 80 85 Corn 60 80 75 60 Holcus 100 100 100 100 Morning Glory 100 100 100 100

RO 114254 Bl

Compound no. 61 62 63 64 Rocinante 100 100 100 100 Thistle-priest 100 100 100 100 Tail fox 70 95 75 80 Tail fox green 100 100 100 100 Johnson's leg 100 100 95 90 Compound no. 65 66 67 68 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 35 40 40 95 Wheat 90 0 10 20 Corn 70 20 20 60 Holcus 100 95 100 100 Morning Glory 100 80 100 100 Rocinante 100 100 95 100 Thistle-priest 100 100 100 100 Tail fox 85 10 10 70 Tail fox green 100 95 80 100 Johnson's leg 100 - 70 95 Compound no. 69 70 71 72 Quantity (kg / ha) □ 3 0.3 0.3 0.3 Species soy 80 80 95 60 Wheat 100 100 100 100 Corn 100 100 100 100 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 100 100 100 100 Tail fox 95 80 80 85 Tail fox green 100 100 100 100 Johnson's leg 100 100 100 100

RO 114254 Bl

Compound no. 73 74 75 76 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 60 50 85 85 Wheat 1QO 85 50 50 Corn 100 100 100 100 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 90 100 100 Thistle-priest 100 90 100 60 Tail fox 100 95 80 100 Tail fox green 100 90 100 100 Johnson's leg 95 70 95 85 Compound no. 77 78 79 80 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 15 60 70 50 Wheat 20 50 70 85 Corn 50 80 100 100 Holcus 95 100 80 100 Morning Glory 100 100 100 100 Rocinante 100 0 90 Thistle-priest 90 100 90 90 Tail fox 10 20 15 40 Tail fox green 10 95 70 100 Johnson's leg 20 85 85 90 Compound no. 81 82 83 84 Quantity (kg / ha) 0.25 0.25 0.25 0.25 Species soy 85 70 50 95 Wheat 95 70 15 20 Corn 100 80 70 50 Holcus 100 95 40 30 Morning Glory 100 100 40 80

RO 114254 Bl

Compound no. 81 82 83 84 Rocinante 90 10 15 Thistle-priest 80 85 60 85 Tail fox 95 90 5 0 Tail fox green 100 100 85 60 Johnson's leg 85 80 40 50 Compound no. 85 86 87 88 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 95 100 95 80 Wheat 45 90 40 85 Corn 100 85 75 100 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 100 100 80 100 Tail fox 75 95 90 90 Tail fox green 100 90 95 100 Johnson's leg 100 95 95 100 Compound no. 89 90 91 92 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 95 100 100 100 Wheat 95 95 100 40 Corn 100 100 100 75 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 100 95 ND 100 Tail fox 100 100 80 90 Tail fox green 100 100 100 100 Johnson's leg 100 100 100 100

RO 114254 Bl

Compound no. 93 94 95 96 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 90 100 100 100 Wheat 100 85 90 95 Corn 100 75 95 100 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 100 100 95 100 Tail fox 100 100 100 95 Tail fox green 100 90 100 100 Johnson's leg 100 100 100 100 Compound no. 97 98 99 100 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 100 85 60 90 Wheat ND 40 40 30 Corn 80 70 70 95 Holcus 100 100 100 100 Morning Glory 100 100 100 100 Rocinante 100 100 100 100 Thistle-priest 100 100 100 100 Tail fox 80 30 30 70 Tail fox green 90 90 70 80 Johnson's leg 95 90 70 95 Compound no. 101 102 103 104 Quantity (kg / ha) 0.3 0.3 0.3 0.3 Species soy 80 90 95 100 Wheat 10 70 100 90 Corn 90 80 95 100 Holcus 100 100 100 100 Morning Glory 100 100 100 100

RO 114254 Bl

Compound no. 101 102 103 104 Rocinante 100 100 100 100 Thistle-priest 100 85 100 100 Tail fox 40 80 60 20 Tail fox green 90 100 100 100 Johnson's leg 100 100 100 100

Claims (11)

1. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl) -phenoxy] -alkanoates, characterized in that they have the general formula (I): Z * Yk X Z. ξ, c 1/ \ 4 ff --- ⁰ 2320 47 And 6 " 5 A-0 ^X 3 ^-7 > (1) 2325 A II in which: AesteR-C-CH- I R · Q is 4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5- (1H) -on-1-yl, or 1-methyl-6-2330 trifluoromethyl-2,4 - (1H, 3H] -pyrimidin-dion-3-yl; R is hydrogen; M, lower alkyl, cycloalkyl, lower alkenyl or lower alkynyl, each optionally substituted with one or more chlorine, fluorine, or / CHR ₇ - (CH ₂ ) _m O / _n R ₈ ; R 'is hydrogen or methyl; R is OR or amino, phenylamino, lower alkylamino, lower alkenylamino, alkoxyamino, cyano or lower alkyl, lower haloalkyl, or phenylsulfonylamino 2335. formula - Lower N -alkyl] -SO ₂ R _g or -NHSO ₂ R _g ; R ₇ is hydrogen or methyl; R ₈ is lower alkyl; R _g is lower alkyl, lower haloalkyl, or phenyl; X is hydrogen, fluorine, methyl or chlorine; Y is hydrogen; W is oxygen or sulfur; Z is hydrogen, fluorine, chlorine, bromine, lower alkyl or methoxy; Z 'is hydrogen, fluorine or chlorine; Z and Z 'together may be a group - (CH ₂ ) ₄ - to form a tetrahydro-2340 naphthyl radical; m is O to 2, and n is 1 to 6; M is sodium, potassium or ammonium; and the group A0- may be in position 2, 3, or 4 of the phenyl ring. 2. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl) -phenoxy] -alkanoates according to claim 1, characterized in that, in general formula (I), R is -OH; X is hydrogen, fluorine or chlorine; and Z is hydrogen, chlorine or lower alkyl. 2345 3. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl] -phenoxy] -alkanoates according to claim 1, characterized in that, in general formula (I), R is lower alkyl, lower chloralalkyl, or - / CHR ₇ - (CH ₂ ] _m 0 / _n R ₈ ; R 'is methyl; RO 114254 Bl Z is in position 4-; Z 'is hydrogen or chlorine at position 3-; m is Q or 1, and n is 1 to 3; and the AO- group is in position 2- of the phenyl ring. 4. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl] -phenoxy] -alkanoates according to claims 1 and 3, characterized in that in general formula (I), Q is 4-difluoromethyl-4,5-dihydro. -3-methyl-1,2,4-triazol-5- (1H) -on-1-yl; R is methyl or CH ₃ 0 (CH ₂ ) ₂ -0- (CH ₂ ) ₂ -; and X is fluorine. 5. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl] -phenoxy] -alkanoates according to claims 1 and 4, characterized in that, in the general formula (I), W is oxygen and Z 'is hydrogen. 6. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl) -phenoxy] -alkanoates according to claims 1 and 5, characterized in that in general formula (I), R is methyl, and Z is ethyl, methyl, methylethyl or chlorine, or R is 2- (2-methoxyethoxy) ethyl, and Z is methyl. 7. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl) -phenoxy] -alkanoates according to claims 1 and 4, characterized in that in general formula (I), R and Z are each methyl, W is sulfur, and Z 'is hydrogen. 8. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl] -phenoxy] -alkanoates according to claims 1 and 3, characterized in that in general formula [I], Q is 1-methyl-6-trifluoro-methyl -2,4- (1H, 3H) -pyrimidindione-3-yl, R is methyl, 2,2,2 trichloroethyl, or CH ₃ O (CH ₂ ] ₂ -0- (CH ₂ ) ₂ -, W is oxygen, X is hydrogen or fluorine, and Z 'is hydrogen. 9. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl) -phenoxy] -alkanoates according to claims 1 and 8, characterized in that in general formula (I), R and Z are each methyl and X is hydrogen or fluorine, or R is methyl, X is hydrogen and Z is ethyl, or R is methyl, X is fluorine and Z is ethyl. 10. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl) -phenoxy] -alkanoates according to claims 1 and 8, characterized in that, in general formula (I), R is 2,2,2-trichloroethyl, X is hydrogen and Z is methyl, or R is 2,2,2 trichloroethyl, X is hydrogen and Z is ethyl. 11. Substituted derivatives of 2 - [(4-heterocyclic-phenoxymethyl) -phenoxy] -alkanoates according to claim 1, characterized in that they are used in the form of an herbicidal composition in admixture with an agriculturally acceptable carrier for controlling the growth of unwanted plants by applying where they grow, or believe they will grow, a herbicide-efficient amount.